Poro~ilo o delu 2008 Annual report 2008

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Poro~ilo o delu 2008

Annual report 2008

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Zalo`il / Published by: Kemijski in{titut Ljubljana, Hajdrihova 19, SI-1001 Ljubljana

Uredili / Edited by: Brigita Pirc, Lucija Kramberger (bibliografija / bibliography)

Fotografije / Photo: Arhiv Kemijskega in{tituta / Archive of the National Institute of Chemistry

Oblikovanje ovitka / Design: Infiniti d.o.o., Ljubljana

Tisk / Printed by: Tiskarna Littera picta d.o.o.

Ljubljana, 2009

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Kazalo

Beseda direktorja ... 5

Poslanstvo Kemijskega in{tituta ... 7

Organizacijska shema ... 8

Vodstvo in{tituta ... 11

Finance ... 12

Prihodki Kemijskega in{tituta ... 14

Zaposleni ... 15

Doktorati, magisteriji in diplome v letu 2008 ... 16

Objave v letu 2008 ... 18

Mednarodno sodelovanje ... 21

Nagrade in priznanja podeljena sodelavcem in{tituta v letu 2008 ... 23

Zaposleni v splo{nem sektorju ... 27

Laboratorij za molekularno modeliranje in NMR spektroskopijo ... 29

Laboratorij za spektroskopijo materialov ... 45

Laboratorij za kemometrijo ... 55

Laboratorij za analizno kemijo ... 71

Laboratorij za kemijo, biologijo in tehnologijo vod ... 85

Laboratorij za prehrambeno kemijo ... 95

Laboratorij za polimerno kemijo in tehnologijo ... 105

Laboratorij za organsko sintezo in kemijo zdravil ... 117

Laboratorij za anorgansko kemijo in tehnologijo ... 121

Laboratorij za elektrokemijo materialov ... 131

Laboratorij za biosintezo in biotransformacijo ... 141

Laboratorij za biotehnologijo ... 151

Laboratorij za katalizo in reakcijsko in`enirstvo ... 165

Laboratorij za procesno in`enirstvo ... 173

Nacionalni center za NMR spektroskopijo visoke lo~ljivosti - lokacija KI ... 181

Center za validacijske tehnologije in analitiko (CVTA) ... 191

Izbrana bibliografija v letu 2008 ... 195

Kazalo

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Word of the Director ... 5

The Mission of the National Institute of Chemistry ... 7

Organisation Chart ... 9

Institute Management ... 11

Finances ... 13

Revenues of the National Institute of Chemistry ... 14

Personnel ... 15

Doctoral, Master’s and Graduate Theses ... 16

Published Works in Year 2008 ... 18

International Cooperation ... 21

Awards amd Recognition 2008 ... 23

General Sector - Employees ... 27

Laboratory for Molecular Modelling and NMR Spectroscopy ... 29

Laboratory for Spectroscopy of Materials ... 45

Laboratory of Chemometrics ... 55

Analytical Chemistry Laboratory ... 71

Laboratory for Chemistry, Biology and Technology of Water ... 85

Laboratory for Food Chemistry ... 95

Laboratory for Polymer Chemistry and Technology ... 105

Laboratory for Organic and Medicinal Chemistry ... 117

Laboratory for Inorganic Chemistry and Technology ... 121

Laboratory for Materials Electrochemistry ... 131

Laboratory for Biosynthesis and Biotransformation ... 141

Laboratory of Biotechnology ... 151

Laboratory for Catalysis and Chemical Reaction Engineering ... 165

Laboratory for Chemical Process Engineering ... 173

National Centre for High Resolution NMR Spectroscopy - Location NIC ... 181

Centre for Validation Technologies and Analytics (CVTA) ... 191

Selected Bibliography in Year 2008 ... 195

Index

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Beseda direktorja Word of the Director

Dear Colleagues and all those of you interested in following the activities of the National Insti- tute of Chemistry,

In front of you is the Annual Report of the Na- tional Institute of Chemistry for 2008. As al- ways, the report is in the lexicographical form.

It contains all of the basic data regarding the Institute, as well as the most important achievements of particular departments.

For National Institute of Chemistry, 2008 was characterized by variety. While research and development results cannot really be divided up by years, we can proudly say that the »harvest«

for 2008 was very solid. Under the leadership of Dr. Roman Jerala, our researchers succeeded in discovering the second binding site for RNA in TL3, which resulted in the publication of their work in the prestigious journal Nature Struc- tural and Molecular Biology.

In terms knowledge transfer to industry, one must single out the technology of wood waste liquefaction developed by Dr. Matja` Kunaver and collaborators. Special mention is due both for the scope of the project, as well as for the cutting edge topic and its fast rate of knowledge transfer.

Spo{tovane kolegice, kolegi, vsi tisti, ki z zanimanjem spremljate Kemijski in{titut, Pred vami je letno poro~ilo za leto 2008. Kot doslej, je tudi to poro~ilo po stilu leksikografsko.

V njem so zajeti vsi bistveni podatki o in{titutu, predstavljeni so najve~ji dose`ki posameznih oddelkov.

Leto 2008 je bilo za Kemijski in{titut pestro.

Rezultate na raziskovalno razvojnem podro~ju je neprimerno predal~kati po letih, pa vendar lahko re~emo, da je bila ravno v letu 2008 `etev zelo obilna. Na{im raziskovalcem pod vodstvom prof. dr. Romana Jerale je uspelo odkriti drugo vezavno mesto za RNA v TL3, kar je omogo~ilo objavo v tako presti`ni reviji kot je Nature Struc- tural and Molecular Biology.

Pri prenosu znanja v gospodarstvo je potrebno posebej izpostaviti tehnologijo uteko~injanja lesnih odpadkov, ki jo je s sodelavci razvil dr.

Matja` Kunaver, tako zaradi obse`nosti projekta, kot tudi zaradi aktualnosti teme in hitrega tempa pri prenosu znanja.

Na{e raziskovalke in raziskovalci so tudi izvrstni mentorji. O tem pri~ajo mnoga priznanja, ki so jih v prej{njem letu prejeli njihovi varovanci.

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Our researchers have also been excellent mentors. Proof can be found in the many awards and recognitions received by their students in 2008.

The now traditional prestigious Pregl Prizes of the National Institute of Chemistry were also awarded in 2008. We are pleased to announce that the recipient of the Grand Pregl Prize was our colleague Prof. Dr. Boris Orel. Professor Orel received the prize for his exceptional achievements in the field of surface functionalization.

Some examples of his work are the use of coat- ings for solar collectors, which allows the surface of the collector to self-clean when it rains, and cotton fabrics that repel water and oil.

In the past year, Dr. Janko @mitek, head of the Centre for Validation Technologies and Analytics, left the Institute. Many thanks to Dr.

@mitek for his development of new forms of cooperation with industry. We wish his succes- sor as head (although still temporary), Dr.

Alenka Wondra Golc, success in her work.

In April, Prof. Miran Gaber{~ek took over the leadership of the Laboratory for Materials Electrochemistry. We would also like to wish Prof. Gaber{~ek, a long-term collaborator of the laboratory, the best of luck in his future research.

Also in April 2008, the mandate of the previous director of the National Institute of Chem- istry, Dr. Peter Venturini, ended. The results achieved in 2008 are undoubtedly due in large measure to his leadership and setting of direc- tions in previous years. We would like to thank him for all of his hard work and wish him the best of successes in his future career.

Finally, I would like to thank all the people who work at the National Institute of Chemistry, who each contributed in their own way to the results presented in this report, as well as all of our partners outside of the Institute for their excellent cooperation.

Professor Janko Jamnik, PhD Director

V letu 2008 so bile `e tradicionalno podeljene presti`ne Preglove nagrade Kemijskega in{tituta.

Veseli smo, da je prejemnik Velike Preglove nagrade, prof. dr. Boris Orel, na{ sodelavec. Prof.

Orel je nagrado prejel za izjemne dose`ke na podro~ju funkcionalizacije povr{in. Primer so premazi za son~ne sprejemnike, ki omogo~ajo, da se ob de`ju povr{ina sprejemnika sama

»o~isti« ter bomba`ne tkanine, ki odbijajo vodo in olja.

V preteklem letu se je od in{tituta poslovil vodja Centra za validacijske tehnologije in analitiko, dr. Janko @mitek. Hvala dr. @mitku za utiranje novih oblik sodelovanja z industrijo. Veliko uspeha za`elimo novi (zaenkrat {e za~asni) vodji, dr. Alenki Wondra Golc.

V aprilu je prof. dr. Miran Gaber{~ek prevzel vodenje Laboratorija za elektrokemijo materialov. Tudi prof. Gaber{~ku, ve~letnemu sodelavcu laboratorija, `elimo sre~no roko pri nadaljnjih raziskavah.

Prav tako v aprilu 2008 je potekel mandat prej{njemu direktorju, dr. Petru Venturiniju.

Gotovo so rezultati leta 2008 v veliki meri zasluga njegovega vodenja in postavljanja kretnic v preteklih letih. Za vlo`eni trud se mu zahvaljujemo in `elimo ~im ve~ uspehov v bodo~i karieri.

Ob koncu se `elim zahvaliti prav vsem sode- lavkam in sodelavcem Kemijskega in{tituta, ki so vsak na svoj na~in pripomogli k rezultatom, zbranim v tem poro~ilu, ter vsem na{im partnerjem za odli~no sodelovanje.

Prof. dr. Janko Jamnik Direktor

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Poslanstvo Kemijskega in{tituta The Mission of the National Institute of Chemistry

Poslanstvo Kemijskega in{tituta

The Mission of the National Institute of Chemistry

- Kemijski in{titut je v Sloveniji vodilna in v svetu prepoznavna raziskovalna organizacija na podro~ju kemije in sorodnih disciplin.

- Z raziskovalnim delom in moderno infra- strukturo zagotavlja vrhunske znanstveno - raziskovalne dose`ke, vzgojo kadrov in prenos novih znanj v gospodarstvo.

- Kemijski in{titut s svojim delom pomembno prispeva h gospodarskemu napredku in izbolj{anju kakovosti `ivljenja v Sloveniji.

- The National Institute of Chemistry is Slovenian leading and worldwide known research institution in the field of chemistry and related disciplines.

- Performed research and modern infra- structure enables top-level scientific research achievments, nurturing new human potentials and transferring knowledge into the economy.

- The results of National Institute of Chemistry substantially contribute to the economic growth and improvement of quality of life in Slovenia.

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Organizacijska shema

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Organizacijska shema Organisation Chart

Organisation Chart

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Vodstvo in{tituta Institute Management

Vodstvo in{tituta

Institute Management

VODSTVO / MANAGEMENT - Direktorja / Directors

doc. dr. Peter VENTURINI (do / till 18.4.2008) prof. dr. Janko JAMNIK (od / since 19.4.2008) - Pomo~nici direktorja /

Assistant directors mag. Renata VUGA

Jo`i ^E[NOVAR (v.d. pomo~nice direktorja / Acting assistant director)

- Svetovalec direktorja / Councellor to the director

doc. dr. Janko @MITEK (do / till 31.8.2008)

^LANI UPRAVNEGA ODBORA / BOARD OF GOVERNORS

- dr. Matej Penca, predsednik / president - prof. dr. Janez Plavec, podpredsednik / vice-

president

- dr. Gregor Gomi{~ek - prof. dr. Roman Jerala

- prof. dr. Tamara Lah (do / till 15.10.2008) - akademik prof. dr. Janez Levec (od / since

16.10.2008) - dr. Brina Ornik - mag. Bogo [est - prof. dr. Toma` [olmajer - doc. dr. Ale{ [trancar

^LANI ZNANSTVENEGA SVETA / SCIENTIFIC COUNCIL

- prof. dr. Janko Jamnik, predsednik / president (do / till 18.4.2008)

- prof. dr. Albin Pintar, predsednik / president (od / since 17.7.2008)

- prof. dr. Ven~eslav Kau~i~, podpredsednik / vice-president

- dr. Franc Avbelj

- prof. dr. Branko Bor{tnik

- prof. dr. Miran Gaber{~ek (od / since 12.6.2008)

- prof. dr. Roman Jerala - prof. dr. Janez Plavec - prof. dr. Milenko Ro{

- izr. prof. dr. Majda @igon

- doc. dr. Peter Venturini, direktor - ~lan po funkciji / member by function (do / till 18.4.2008)

- prof. dr. Janko Jamnik, direktor - ~lan po funkciji / member by function (od / since 19.4.2008)

^ASTNI ^LANI / HONORARY MEMBERS - prof. dr. Igor BELI^, 19. 12. 1986 - dr. Marta BLINC, 19. 12. 1986 - prof. dr. Bojan DR@AJ, 19. 12. 1986 - dr. Jo`e FEGE[, 19. 12. 1986

- prof. dr. Vera JOHANIDES, 19. 12. 1986 - prof. dr. Roman MODIC, 19. 12. 1986 - prof. dr. Tihomir NOVAKOV, 19. 12. 1986 - prof. dr. Robert LAFFERTY, 15. 6. 1994 - prof. dr. Walter STEINER, 15. 6. 1994 - prof. dr. D. Luc MASSART, 8. 3. 1995 - prof. dr. John R. HELLIWELL, 21. 10. 1996 - prof. dr. Joachim MAIER, 17. 4. 1996 - prof. dr. Du{an HAD@I, 9. 10. 2001 - prof. dr. Joseph WANG, 15. 6. 2007 - prof. dr. Milan RANDI], 27. 9. 2007

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Finance

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Finance Finances

Finances

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Prihodki Kemijskega in{tituta

Revenues of the National Institute of Chemistry

SLIKA

Prihodki Kemijskega in{tituta v mio EUR.

FIGURE

Revenues of the National Institute of Chemistry in million euros.

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Zaposleni Personnel

Na dan 31. 12. 2008 je bilo na Kemijskem in{titutu 263 zaposlenih, od tega 111 doktorjev znanosti, 6 magistrov, 104 z visoko izobrazbo, 11 z vi{jo izobrazbo, 22 s srednjo in 9 z ni`jo izobrazbo. [tevilo zaposlenih se je glede na predhodno leto pove~alo za 2,7%, predvsem na ra~un uspe{nih prijav na razpis za mlade raziskovalce.

On December 31, 2008, we have recorded 263 employees with the following degree of education: Ph.D. (111), Master degree (6), Bachelor degree (104), Associate degree (11), secondary school (22) and less than secondary school (9). Compared to the previous year the number of employees rose by 2,7%,mainly due to a number of successful applications for the

“Young Researcher” tender.

SLIKA

Izobrazbena struktura zaposlenih na Kemijskem in{titutu v letu 2008.

FIGURE

Employees level of education at the National Insti- tute of Chemistry in 2008.

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Doktorati, magisteriji in diplome v letu 2008 Doctoral, Master’s and Graduate Theses in Year 2008

DOKTORATI / DOCTORAL THESES Jemec Anita 27.3.2008

Iva Hafner Bratkovi~ 31.3.2008 Kurbus Tanja 24.4.2008 Cevec Mirko 8.5.2008 Urbi~ Tja{a 16.5.2008 Konc Janez 21.5.2008 [terk Damjan 4.7.2008

SLIKA

Doktorati, magisteriji in diplome v letih 2000 / 2008.

FIGURE

Ph.D., M.Sc., and B.Sc. theses in years 2000 / 2008.

Peternel [pela 1.9.2008 Va{l Jo`ica 26.8.2008 Gri~ar Maja 16.10.2008 Zorko Mateja 29.9.2008 Mazaj Matja` 22.10.2008 [olar Tina 24.10.2008 Slavec Marija 17.10.2008 Japelj Bo{tjan 28. 10. 2008

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Doktorati, magisteriji in diplome v letu 2008 Doctoral, Master’s and Graduate Theses in Year 2008

[TEVILO DIPLOM, MAGISTERIJEV, DOKTORATOV, MENTORSTEV IN KOMENTORSTEV S STRANI ZAPOSLENIH NA KEMIJSKEM IN[TITUTU

NUMBER OF B. Sc., M. Sc., Ph. D. THESES, MENTORSHIPS AND COMENTORSHIPS BY EMPLOYEES OF NATIONAL INSTITUTE OF CHEMISTRY

1 magisterij / Master’s Thesis 14 doktoratov / Doctoral Theses

12 mentorstev pri diplomah / Mentorships of Undergraduate Theses 5 mentorstev pri magisterijih / Mentorships of Master’s Theses 14 mentorstev pri doktoratih / Mentorships of Doctoral Theses

18 komentorstev pri diplomah / Comentorships of Undergraduate Theses 1 komentorstvo pri magisteriju / Comentorship of Master’s Thesis 1 komentorstvo pri doktoratu / Comentorship of Doctoral Thesis

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Objave v letu 2008

Published Works in Year 2008

SLIKA

Objavljena dela (~lanki, knjige, poglavja, patenti) v letih 2000 / 2008.

FIGURE

Published works (papers, books, chapters, patents) in years 2000 / 2008.

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Objave v letu 2008 Published Works in Year 2008

Institute bibliography for 2008 ANALYTICAL DATA (typology COBISS / laboratories) Bibliografija in{tituta v letu 2008 ANALIT^NI PODATKI (tipologija COBISS / laboratoriji)

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Mednarodno sodelovanje International Cooperation

Mednarodno sodelovanje

International Cooperation

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Nagrade podeljene sodelavcem in{tituta v letu 2007 Awards Given To Collaborators with the Institute in 2007

Nagrade in priznanja podeljena sodelavcem in{tituta v letu 2008

Awards and Recognition of Collaborators of the National Institute of Chemistry in 2008

Veliko Preglovo nagrado Kemijskega in{tituta za raziskovalno delo je prejel prof.

dr. Boris Orel, 19. 6. 2008.

The Grand Pregl Award of the National Institute of Chemistry for Research Work was awarded to Prof. Dr. Boris Orel, June 19^th 2008.

Ministrica za visoko {olstvo, znanost in tehnologijo Mojca Kucler Dolinar izro~a Veliko Preglovo nagrado prof. dr. Borisu Orlu.

Minister for Higher Education, Science and Techno- logy Mojca Kucler Dolinar awards the Grand Pregl Award to Professor Boris Orel.

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Preglovo nagrado Kemijskega in{tituta za izjemno doktorsko delo na podro~ju kemije in sorodnih ved sta 3. 12. 2008 prejela:

- dr. Urban Bren (Laboratorij za molekularno modeliranje in NMR spektroskopijo): “Ra~u- nalni{ke simulacije proste energije pri obravnavi stabilnosti in reaktivnosti DNA”;

mentor: doc. dr. Janez Mavri, somentor: prof.

dr. Jo`e Koller in

- dr. Du{an Strm~nik (Laboratorij za elektrokemijo materialov): “Aktivna mesta za reakcije v PEM gorivnih celicah v modelnih in realnih sistemih”; mentorja: doc. dr. Miran Gaber{~ek in dr. Nenad M. Markovi}.

Prof. dr. Radovan Komel (vodja Laboratorija za biosintezo in biotransformacijo) je ob obele`enju 25. obletnice delovanja Slovenskega biokemijskega dru{tva, 12. 11. 2008, prejel prvo Lapanjetovo nagrado.

Dr. Urban Bren iz Laboratorija za molekularno modeliranje in NMR spektroskopijo je 3. 12.

2008 prejel nagrado Maksa Samca za doktorsko disertacijo s podro~ja kemije:

“Ra~unalni{ke simulacije proste energije pri obravnavi stabilnosti in reaktivnosti DNA”;

mentor: doc. dr. Janez Mavri, somentor: prof.

dr. Jo`e Koller.

Sodelavci Laboratorija za biotehnologijo, prof.

Roman Jerala, dr. Mojca Ben~ina, Monika Cigli~, Karolina Ivi~ak in Nina Pirher so bili, skupaj s prof. Simonom Horvatom z Biotehni{ke fakultete Univerze v Ljubljani, mentorji ekipi {tudentov Univerze v Ljubljani, ki se je na mednarodnem tekmovanju raziskovalnih projektov (iGEM) na presti`ni univerzi MIT v Cambridge-u, ZDA, uvrstila v finale, osvojila prvo mesto v generalni razvrstitvi (Grand Prize) in dosegla tudi prvo mesto na podro~ju zdravja in medicine ter zlato medaljo (9. 11. 2008).

The Pregl Award of the National Institute of Chemistry for outstanding doctoral work in the field of chemistry and related sciences was awarded to:

- Dr. Urban Bren (Laboratory for Molecular Modeling and NMR Spectroscopy): “Free- Energy Computer Simulations of DNA Stability and Reactivity”; mentors: Dr. Janez Mavri, Assist. Prof., comentor: Prof. Dr. Jo`e Koller and

- Dr. Du{an Strm~nik (Laboratory for Materials Electrochemistry): “Active sites for PEM fuel cell reactions in model and real systems”; mentors: Prof. Dr. Miran Gaber{~ek and Dr. Nenad M. Markovi}.

(December 3^rd, 2008.)

At 25^th anniversary of the Slovenian Biochemical Society Prof. Dr. Radovan Komel was awarded with a special award named after Prof.

Dr. Savo Lapanje (November 12^th 2008).

Dr. Urban Bren (Laboratory for Molecular Modeling and NMR Spectroscopy): received the Maks Samec Award for doctoral work in the field of chemistry: “Free-Energy Compu- ter Simulations of DNA Stability and Reactivity”;

mentors: Dr. Janez Mavri, Assist. Prof., comentor: Prof. Dr. Jo`e Koller (December 3rd 2008).

Members of the Laboratory of Biotechnology, Prof. Roman Jerala, Dr. Mojca Ben~ina, Monika Cigli~, Karolina Ivi~ak and Nina Pirher were, together with Prof. Simon Horvat from the Biotechnical Faculty, University of Ljubljana, mentors of a student team of University of Ljubljana, which participated in an international competition of research projects iGEM at the MIT in Cambridge, USA, won Grand Prize in the general ranking and golden medal for the first place in the field of Health and Medicine (November 9^th 2008).

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Nagrade podeljene sodelavcem in{tituta v letu 2007 Awards Given To Collaborators with the Institute in 2007

Zmagovalna ekipa {tudentov ljubljanske univerze skupaj z mentorji, pred Massachusetts Institute of Technology, Cambridge, ZDA

The winning team of students with their mentors in front of the Massachusetts Institute of Technology, Cambridge, USA

Prof. dr. Roman Jerala, dr. Mojca Ben~ina, dr. Mateja Man~ek – Keber, Gabriela Panter in Karolina Ivi~ak (mentorji iz Laboratorija za biotehnologijo) so prejeli nagrado SOVA za visoko{olsko didaktiko, ki jo podeljuje Slovensko dru{tvo za visoko{olsko didaktiko; 4.

3. 2008.

Mlada raziskovalka Ljerka Lah (Laboratorij za biosintezo in biotransformacijo), je zmagala na mednarodnem tekmovanju priprave najbolj{ega poslovnega na~rta, kako prenesti akademska biotehnolo{ka odkritja v industrijo. Premagala je konkurenco 45. izbranih {tudentov z vodilnih evropskih univerz. (Novartisov BioCamp; v Baslu, [vici, 28.-30. 8. 2008).

Prof. dr. Miran Gaber{~ek in sodelavci iz Laboratorija za elektrokemijo materialov so prejeli nagrado “2Most Excellent Paper” na najve~jem baterijskem simpoziju “14^th Inter-

Prof. Roman Jerala, Dr. Mojca Ben~ina, Dr. Mateja Man~ek – Keber, Gabriela Panter and Karolina Ivi~ak won the Prize SOVA for higher education didactics, awarded by the Slovenian Society for Didactics in Higher Education (March 4^th 2008).

The young researcher Ljerka Lah (Laboratory for biosynthesis and biotransformation) was the winner of international competition in preparing the best business plan on how to transfer academic biotechnology discoveries to industry. She emerged best from among 45 selected students from leading European universities. (Novartis, Biocamp, Basel, Switzerland, 28-30. Aug. 2008).

At the biggest battery conference “14^th International Meeting on Lithium Batteries«, Tianjin, China, 2008 (more than 1000 participant), Miran Gaber{~ek et al.

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national Meeting on Lithium Batteries«, Tianjin, Kitajska, 2008 (preko 1000 udele`encev).

Nina Pirher, mlada raziskovalka Laboratorija za biotehnologijo, je prejela nagrado revije Nature Reviews Immunology za najbolj{i poster na znanstveni konferenci o naravni imunosti (Lizbona, Portugalska, 20. 10. 2008).

38. Krkine nagrade 2008; Novo mesto, 17.

10. 2008

Krkine nagrade za posebne dose`ke na podro~ju raziskovalnega dela:

- dr. Damjan [terk: “Novi kiralni ligandi za asimetri~ne redukcije”; mentor: prof. dr. Boris [ket, somentorica: dr. Barbara Mohar.

Krkine nagrade:

- dr. Iva Hafner Bratkovi~: “Vpliv strukturnih sprememb prionskega proteina na infek- tivnost in vezavo specifi~nih reagentov”;

mentor: prof. dr. Roman Jerala

- Marko Trajkovski: “[tudij interakcij kationov z DNA aptamerom trombina”; mentor: dr.

Primo` [ket, somentor: prof. dr. Janez Plavec - dr. Mateja Zorko: “Nevtralizacija endo- toksina z novimi antimikrobnimi u~inko- vinami”, mentor: dr. Primo` Pristov{ek.

Pre{ernove nagrade {tudentom; december 2008

- Ana Krofli~: “Preu~evanje fizikalno-kemijskih lastnosti polimorfnih oblik klaritromicina”, diplomsko delo; mentor: dr. Marjan Bele - Alja Oblak: ”Vpliv zamenjave aminokislin 82,

85 in 87 na aktivnost proteina MD-2”, diplomsko delo; mentor: prof. dr. Gregor Anderluh, somentor: prof. dr. Roman Jerala - Ota Fekonja: “Vpliv dimerizacije domen Toll/

interleukin-1 receptorjev na signalizacijo Tollu podobnih receptorjev”, diplomsko delo;

mentor: prof. dr. Gregor Anderluh, somentor:

prof. dr. Roman Jerala.

received an award for the »Most Excellent Paper”.

Young researcher of the Laboratory of Biotech- nology, Nina Pirher, won the best poster prize at the scientific conference on innate immunity, which was awarded together with one year subscription by the journal Nature Reviews Immunology (Lisboa, Portugal, October 20^th 2008).

38. Krka Prize 2008; Novo mesto, October 17^th 2008

Krka Prizes for Special Achievements in Research:

- Dr. Damjan [terk, “New chiral ligands for asymmetric reductions”, mentor: Prof. Dr.

Boris [ket, comentor: Dr. Barbara Mohar.

Krka Prize:

- Dr. Iva Hafner Bratkovi~: “Influence of prion protein atructural change on infectivity and binding of specific reagents”, mentor:

Prof. Dr. Roman Jerala

- Marko Trajkovski: “Studies of cationa interactions with DNA aptamer of thrombin”, mentor: Dr. Primo` [ket, comentor: Prof. Dr.

Janez Plavec

- Dr. Mateja Zorko: “Neutralization of endotoxin by novel antimicrobial sub- stances”, mentor: Dr. Primo` Pristov{ek.

The Pre{eren Prize to students; December 2008

- Ana Krofli~: “Physicochemical properties of polymorphic forms of clarithromycin”, graduation thesis; mentor: Dr. Marjan Bele - Alja Oblak: “The effect of mutations of

amino acid residues 82, 85 and 87 on the activity of MD-2”, graduation thesis; mentor:

Prof. Dr. Gregor Anderluh, comentor: Prof.

Dr. Roman Jerala

- Ota Fekonja: “The effect of Toll/interleukin- 1 receptor domain dimerization on Toll-like receptor signaling”, graduation thesis;

mentor: Prof. Dr. Gregor Anderluh, comentor:

Prof. Dr. Roman Jerala.

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Splo{ni sektor General Sector

Zaposleni v splo{nem sektorju General Sector - Employees

UPRAVA / ADMINISTRATION Babnik Izidor

Dobnikar Francka Husi} Muharem Merzel Marija Petrov~i~ Vida Zupan~i~ Andreja Pirc Brigita Jezernik Ma{a Svetic Tanja Mrak Velesa

TEHNI^NE DELAVNICE / TECHNICAL SERVICES Vidmar Robert

Ambro` Toni Babnik Gregor Smole Marjan Vrhovec Pavel

RA^UNOVODSTVO, PLAN IN

ANALIZE / ACCOUNTING, PLANNING AND ANALYSES

Dori} Barbara Goren{ek Vedrana Miri~ Maja Oblak Irena Pintari~ Janja Skok Zlatka Skumavc Meta Stritih Radovan Volov{ek Tanja KNJI@NICA / LIBRARY Kramberger Lucija Grah Lilijana

[TIPENDIJE / SCOLARSHIPS Grilc Miha

Miklavi~ [pela Tehovnik Andrej

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Laboratorij za molekularno modeliranje in NMR spektroskopijo Laboratory for Molecular Modelling and NMR Spectroscopy

L01

Laboratorij za molekularno modeliranje in NMR spektroskopijo

Laboratory for Molecular Modelling and NMR Spectroscopy

VODJA / HEAD prof. dr. Branko Bor{tnik

RAZISKOVALCI / RESEARCHERS dr. Franc Avbelj

dr. Urban Bor{tnik dr. Urban Bren

doc. dr. Simona Goli~ Grdadolnik doc. dr. Jo`e Grdadolnik

akad. prof. dr. Du{an Had`i dr. Milan Hodo{~ek prof. dr. Du{anka Jane`i~

dr. Janez Konc doc. dr. Janez Mavri doc. dr. Franci Merzel dr. Gregor Mlin{ek dr. Matej Penca

dr. Ksenija Poljanec doc. dr. Matej Praprotnik dr. Danilo Pumpernik dr. Jernej Stare

prof. dr. Toma` [olmajer dr. Tja{a Urbi~

MLADI RAZISKOVALCI / YOUNG RESEARCHERS Rok Bor{tnar

Matja` Brvar Nejc Carl Martina Glu{i~

Borut Tone Oblak Andrej Perdih Gordana Pirc Mihael Sim~i~

Jernej Zidar

TEHNI^NO OSEBJE / TECHNICAL STAFF Silva Zagorc

PRIPRAVNIKI/TRAINEES Bla` Vehar

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PODRO^JA DEJAVNOSTI Raziskovalni program P1-0012 (B. Bor{tnik)

Molekulske simulacije in bioinformatika - Simulacija encimske katalize

- Kvantno kemijski izra~uni strukturnih in ele- ktronskih parametrov molekul in supramole- kularnih sistemov

- [tudij dinamike tvorbe in razpada medmole- kulskih vezi in dinamike reakcij prenosa ato- ma (atom-transfer reactions)

- Simulacija protonske dinamike in prenosa protona v hidratiranih in vodikovo vezanih sistemih z metodami klasi~ne in kvantne molekularne dinamike

- Prou~evanje strukture in katalitske aktivnosti titanosilikalitnih zeolitnih materialov - [tudij endogene karcinogeneze

- Bioinformatika in {tudij biolo{ke evolucije na molekularni osnovi.

- Statisti~na mehanika

- Z metodo racionalnega na~rtovanja novih zdravilnih u~inkovin na osnovi strukture re-

RESEARCH ACTIVITIES

Research program P1-0012 (B. Bor{tnik) Molecular simulations and bioinformatics - Quantum chemical calculations of structural

and electronic parameters of molecules and supramolecular systems

- Studies of dynamics of formation and decay of intermolecular bonds atom-transfer reactions

- Simulation of proton dynamics and proton transfer reactions in hydrated and hydrogen- bonded systems using the methods of classical and quantum molecular simulations - Studies of structure and catalytic activity of

titanosilicalite zeolites

- Study of endogeneous cancerogenesis - Bioinformatics and study of biological evolu-

tion

- Statistical mechanics

- Structure-based drug design approach is used for mechanistic studies of enzyme inhibition and design of novel bioactive compounds

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ceptorja prou~ujemo mehanizem inhibicije encimov in na~rtujemo nove, potencialno biolo{ko aktivne spojine

Raziskovalni projekt J1-0308 (T. [olmajer)

Strukturno podprto na~rtovanje novih inhibitorjev DNA giraz

Raziskovalni projekt Z1-9779 (J. Stare) Razvoj in optimizacija zeolitnih katalizatorjev z metodami molekulskega modeliranja Raziskovalni program P1-0010 (F. Avbelj) Folding in dinamika biomolekularnih sistemov - Raziskave strukture in dinamike biomolekularnih sistemov (proteinov, ligandov, mem- bran in njihovih kompleksov) z jedrsko mag- netno resonanco, vibracijsko spektroskopijo in z ra~unalni{kimi simulacijami (Monte Car- lo, molekulska dinamika)

- [tudij elektrostatskih interakcij, vodikovih vezi, solvatacije (elektrostatsko sen~enje) in hidrofobnih interakcij v proteinih, v sistemih ligand-receptor in v sistemih biomolekula- membrana

- [tudij energetike in kinetike zvitja proteinov - Razvoj algoritmov za napovedovanje sekun–

darnih in tridimenzionalnih struktur proteinov (problem zvitja proteinov ‘protein folding problem’, strukturna genomika) - Konformacijske {tudije novih u~inkovin v pov-

ezavi z njihovim biolo{kim u~inkom - Razvoj metod vibracijske spektroskopije

(ra~unanje opti~nih konstant iz refleksijskih in ATR spektrov)

- [tudij vodikovih vezi z eksperimentalnimi in teoretskimi metodami

- Razvoj metod jedrske magnetne resonance za dolo~anje konformacije molekul v teko~ini - Uporaba vibracijske spektroskopije in jedrske

magnetne resonance v analizne namene

Research project J1-0308 (T. [olmajer) Structure based design of novel inhibitors of DNA gyrase

Research project Z1-9779 (J. Stare) Design and Optimization of Zeolite Catalysts by Molecular Modeling Methods

Research program P1-0010 (F. Avbelj) Protein folding and dynamics of biomolecular systems

- Studies of structure and dynamics of biomolecular systems (proteins, ligands, mem- branes, and related complexes) using nuclear magnetic resonance, vibrational spectroscopy, and computer simulations (Monte Car- lo, molecular dynamics)

- Studies of electrostatic interactions, hydrogen bonds, solvation (electrostatic screening), and hydrophobic interactions in proteins, lig- and-receptor and ligand-membrane complexes

- Studies of energetics and kinetics of the protein folding process

- Development of algorithms for predicting secondary and three-dimensional structure of proteins (protein folding problem, structural genomics)

- Conformational studies of novel drugs in re- lation with their biological activity

- Development of new methods for vibrational spectroscopy (calculation of optical constants)

- Studies of hydrogen bonding using experimental and theoretical methods

- Development of new methods for conformational studies of molecules by the high-resolution nuclear magnetic resonance spectroscopy

- Application of nuclear magnetic resonance spectroscopy and vibrational spectroscopy in chemical analysis

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SLIKA 1:

http://charmming.org

FIGURE 1:

http://charmming.org Raziskovalni program P1-0002:

(Dr. Du{anka Jane`i~)

Ra~unalni{ko modeliranje strukture in dinamike molekul

Raziskovalna projekta:

J1-6331: (Dr. Du{anka Jane`i~)

Razvoj ra~unalni{kih algoritmov za simulacije makromolekularnih sistemov

J1-9804: (Dr. Franci Merzel)

Ra~unalni{ke simulacije in analiza kolektivnih gibanj biomolekul

Razvoj in uporaba metod za molekularno modeliranje:

- Simplekti~ne metode za simulacijo molekulske dinamike makromolekul

- Kombinacije metod simulacije molekulske dinamike, analize po normalnih na~inih nihanja in kvaziharmonske analize proteinov v raztopinah za {tudij hidratacije proteinov - Razvoj in uporaba QM/MM metod

Research program P1-0002: (Dr.Du{anka Jane`i~)

Computer simulation of molecular structure and dynamics

Research projects:

J1-6331: (Dr. Du{anka Jane`i~)

Computer Algorithms Development for Mac- romolecular Simulation

J1-9804: (Dr. Franci Merzel)

Computer simulations and analysis of collec- tive motions of biomolecules

Development and application of methods for molecular modeling:

- Symplectic methods for molecular dynamics simulations of macromolecules

- Combination of molecular dynamics methods, normal mode vibrational analysis, and quasiharmonic analysis of proteins in solu- tions for studying protein hydration

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- Razvoj ra~unsko u~inkovitih metod za dolo~anje ~asovno odvisne elektronske strukture molekul na osnovi Kohn-Sham-ove for- mulacije teorije gostotnih funkcionalov - Razvoj in aplikacija kvantno kemijskih in

klasi~nih pristopov za izra~un reakcijskih me- hanizmov, predvsem za izra~un ionskih reakcij izocianidov

- Razvoj novih in u~inkovitih ra~unalni{kih topologij za povezovanje osebnih ra~u- nalnikov v ra~unske gru~e

BIBLIOGRAFIJA

27 izvirnih znanstvenih ~lankov 1 pregledni znanstveni ~lanek 2 polemiki, diskusijska prispevka 1 drugo u~no gradivo

3 objavljeni znanstveni prispevki na konferencah

36 objavljenih povzetkov znanstvenih prispev- kov na konferencah

1 objavljeni povzetek strokovnega prispevka na konferenci

2 patentni prijavi

8 predavanj na tujih univerzah 4 prispevki na konferencah brez natisa 5 vabljenih predavanj na konferencah brez

natisa

1 kon~no poro~ilo o rezultatih raziskav 2 diplomi

2 doktorata 3 uredni{tva revij

GLAVNI DOSE@KI V LETU 2008

- [tudirali smo konformacijske preference 13 blokiranih aminokislin (dipeptidov) z uporabo infrarde~e in ramanske spektroskopije.

Uspe{no smo izrabili prednost ~asovne skale, karakteristi~ne za vibracijsko spektroskopijo, kar nam omogo~a spremljanje tudi kratko-

`ivih konformacijskih stanj. Pokazali smo, da sta frekvenca in notranja struktura amidnega traku I (razmerje obeh intrinzi~nih kompo- nent) v spektrih vodnih raztopin dipeptidov odvisni od velikosti dihedralnega kota ϕ. S prikazano analizo amidnega I traku zato ne

- Development and use of QM/MM methods - Development of computationally efficient

methods for determining the time-dependent electronic structure of molecules based on the Kohn-Sham formulation of the density functional theory

- Development and application of quantum chemical and classical approaches for calcu- lating reaction mechanisms, especially calcu- lating the ionic reactions of isocyanides - Development of new and effective network

topologies for connecting personal computers into computational clusters

BIBLIOGRAPHY

27 Original Scientific Articles 1 Review Article

2 Polemics, Discussions 1 Other Educational Material

3 Published Scientific Conference Contri- butions

36 Published Scientific Conference Contri- bution Abstracts

1 Published Professional Conference Contri- bution Abstracts

2 Patent Applications

8 Invited Lectures at Foreign Universities 4 Unpublished Conference Contributions 5 Unpublished Invited Conference Lectures 1 Final Research Report

2 Undergraduate Theses 2 Doctoral Dissertations 3 Journal Editorships

IMPORTANT ACHIEVEMENTS IN 2008 - We studied the conformational preferences

of 13 dipeptides using infrared and Raman spectroscopy. The main advantage of vibrational spectroscopy over NMR is in its much shorter time-scale, which enables determination of the conformational preferences of short-lived states. Accuracy of structure determination using vibrational spectroscopy depends critically on identification of the vibrational parameters that are sensitive to

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SLIKA 2:

(a) podrobnosti vezave spojine 17d v aktivno mesto MurD ligaze. Fo - Fc residualna mapa je narisana pri 3.0σ (zeleno).

(b) vezava spojine 17d v aktivno mesto MurD iz E.

coli

FIGURE 2:

(a) Details of the ligand-binding site in the MurD complex with compound 17d. The Fo - Fc residual map is contoured at 3.0σ (green).

(b) Binding mode of compound 17d in the active site of E. coli MurD.

moremo dolo~iti populacij α_pkonformacij v dipeptidih. Na primeru alanin in valin dipeptidov v vodni raztopini smo pokazali, da je zelo uporabna analiza amidnega traku III v infrarde~ih spektrih in skeletnih nihanj v ra- manskih spektrih. Pokazali smo, da je alanin dipeptid v vodi prete`no v PP_II konformaciji, preostanek pa je v β konformaciji. V dipep- tidu valina je dele` konformacije β pribli`no enak dele`u konformacije PP_II. V obeh primer- ih je dele` α_R konformacije majhen. Predstav- ljeni eksperimentalni podatki povsem ustreza- jo napovedim preferen~nih konformacij mod- ela elektrostatskega sen~enja.

- Dinamiko kratkih, mo~nih vodikovih vezi, ki povezujejo karboksilne skupine z molekula- mi vode v kristalih dihidrata oksalne kisline (α-POX), smo raziskovali z ramansko in infrarde~o spektroskopijo. Za interpretacijo smo rabili izra~une s programom CRYSTAL- 06. Najbolj zanimivi so temperaturni u~inki na obrise vale~nega nihanja O-H, ki se razte- za med 2000 cm^-1 in 1400 cm^-1. Izredno mo~ne spremembe intenzitet nekaterih kom- ponent tega traku ka`ejo na mehanizem samozajetja polaronske ekscitacije. Prej{nje meritve temperaturne in frekven~ne odvisnos- ti ac prevodnosti α-POX-a so bile pripisane tvorbi polaronov.

changes in conformation. We show that the frequencies of Amide I band and the A₁₂ ratio of Amide I components of dipeptides cor- relate with the ³J(H_N, H_α). These two IR vibrational parameters are thus, analogous to

3J(H_N, H_α), indicators for the preference for the dihedral angle ϕ. We also show that the intensities of the components of the Amide III bands in IR spectra and the intensities of the skeletal vibrations in Raman spectra are indicators of populations of the P_II, β, and α_R conformations. The results show that alanine dipeptide adopts predominantly the P_II conformation. The population of the β conformation increases in valine dipeptide. The populations of the α_R conformation are general- ly small. These data are in accord with the electrostatic screening model of conformational preferences.

- The dynamics of short, strong hydrogen bond connecting the carboxylic group to water molecules in the crystal of oxalic acid dihy- drate (α-POX) has been investigated by Ra- man and infrared spectroscopy. The assign- ment of normal modes has been supported by CRYSTAL06 calculations. Most interesting are extremely strong temperature effects on the intensity of the component bands form- ing the complex envelope of the OH stretch- ing band that appears between 2000 cm^-1

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- Zaradi znatnega vpliva kristalne okolice na lastnosti vodikove vezi smo na{e {tudije strukture in dinamike kratkih vodikovih vezi us- merili predvsem v trdno stanje. Z metodo Car- Parrinellove molekulske dinamike smo pokazali, da je kratka vodikova vez v kristalini~nem tetraacetiletanu (TAE) asimetri~na navkljub intrinzi~ni simetri~nosti molekule TAE. Na drugem reprezentativnem sistemu, N-oksidu pikolinske kisline (PANO) v trdnem stanju, pa smo napravili simulacijo konture {irokega protonskega traku, ki ga opazimo v vibracijskem spektru spojine, in pokazali, da je {ir- jenje traku posledica mo~nih sklopitev protonskega gibanja s {tevilnimi inter- in in- tramolekularnimi prostostnimi stopnjami.

Izra~un konture absoprcije protonskega nihanja v vibracijskem spektru temelji na dinami~nem vzor~enju protonskega poten- ciala in predstavlja pomembno novost v ra~unskem modeliranju molekulskih vibracij.

- Titanosilikalitni katalizator TS-1 je industrijsko eden najpomembnej{ih zeolitnih materialov.

Vpra{anje lokacije titanovih mest v TS-1 do danes {e ni bilo zadovoljivo re{eno, prav tako pa so mehanizmi kataliziranih reakcij slabo poznani. Napravili smo periodi~no kvantnomehansko {tudijo preferen~ne lokacije titana na razpolo`ljivih 12 kristalografsko ne- enakih mest. Izra~unane preference se dobro ujemajo z eksperimentalnimi ugotovit- vami, pa tudi z nekaterimi prej{njimi, bolj aproksimativnimi ra~unskimi {tudijami. Zaradi nizkih energijskih razlik med posameznimi izomeri ne gre izklju~iti, da je vezava titana v material odlo~ilno pogojena z entropijskimi faktorji ali pa je celo kineti~no kontrolirana.

Podrobno smo prou~evali tudi mehanizem epoksidacije propena z vodikovim peroksi- dom, ki je ena najpomembnej{ih reakcij, ki jih katalizira TS-1, in ovrednotili vpliv molekul vode, reakcijskega polja topila, elektri~- nega polja in eksplicitne zeolitne okolice na aktivacijsko pregrado in reakcijski mehanizem.

and 1400 cm^-1. Their origin is being sought in self trapped, polaron like excitations. The previously observed temperature and fre- quency dependent ac conductivity of α-POX crystals have been attributed to polaron tun- nelling.

- Our studies of short hydrogen bonds have been mainly focused in the crystalline solid- state environment, since crystal field was found to play a significant role in the structure and dynamics of hydrogen bonds. We simulated the crystalline tetraacetylethane (TAE) with the Car-Parrinello molecular dynamics technique and found that the hydrogen bonding is essentially asymmetric, de- spite the intrinsic chemical symmetry of the TAE molecule. With the same methodology we also simulated the contour of the broad protonic infrared absorption of the short hydrogen bond of picolinic acid N-oxide (PANO) in the solid state. We demonstrated that the band broadening is mainly due to the exten- sive coupling of the proton motion with a number of inter- and intramolecular degrees of freedom. The present approach of simulating the contours of bands in vibrational spectra represents an important novelty in the simulation of molecular vibrations.

- Titanosilicalite catalyst TS-1 is one of the most widely used zeolite materials. However, its detailed structure, especially the location of titanium active sites and the mechanisms of the catalyzed reactions, are still poorly known.

We have performed a fully periodical quantum-mechanical study of the preference order of incorporation of titanium on the twelve available (crystallographically inequivalent) sites. The calculated preference order is in a reasonable agreement with experimental findings and also with some previously published yet more approximate computational studies. Since the energy differences between the site isomers are small, the site preference may be controlled by entropic terms or the titanium substitution can even be governed

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- Izvedli smo ra~unalni{ke simulacije 98 majhnih peptidov dol`ine 6, 8, 10 in 12 aminokis- linskih ostankov proteina G. Iskali smo sta- bilne fragmente. Molekulsko dinamiko zamenjave replik smo izvajali s programom Amber 7. Uporabili smo polje sil parm96 s posplo{enim Bornovim modelom topila (GB/

SA). Ugotovili smo, da je dober kriterij za dolo~evanje strukturiranih fragmentov kon- formacijska entropija in prosta energija posameznega stanja. Velika razlika proste energije med osnovnim in prvim vi{jim stan- jem ter nizka entropija sta zna~ilna za struk- turirane peptide. Veliko strukturiranih peptidov ima strukture podobne nativni. Simulac- ije kraj{ih peptidov so uporabne za ugotav- ljanje mest, kjer se protein pri~ne zvijati, in lahko pripomorejo k bolj{emu napovedovanju strukture proteinov.

- Mur ligaze igrajo pomembno vlogo pri bio- sintezi bakterijskega peptidoglikana in pred- stavljajo privla~ne tar~e za razvoj novih pro- tibakterijskih u~inkovin. Z metodo proteinske kristalografije smo dolo~ili strukturo N-sulfon- il-D-Glu derivatov v kompleksu z encimom MurD iz E. coli. Serija substituiranih naftalen- skih analogov z znanim na~inom vezave v aktivno mesto tega encima je omogo~ila tudi spoznanja o relacijah med strukturo in aktivnostjo (skupaj s sodelavci iz Leka d.d., Ljubljana in Fakultete za farmacijo Univerze v Ljubljani).

- Z uporabo tar~ne molekulske dinamike smo postavili dinami~ni model vezave obeh sub- stratov (ATP in UDP-MurNAc-L-Ala) v njuni vezavni mesti in analizirali zapiranje C-termi- nalne domene MurD.

- S hibridnimi kvantnomehansko/molekul- skomehanskimi metodami (QM/MM) smo {tudirali mehanizem nastanka tetraedri~nega intermediata, ki pogosto predstavlja osnovo za razvoj novih inhibitorjev. Dobljeni molekularni modeli encimske reakcije so v skladu z eksperimentalnim reakcijskim vrstnim re- dom.

kinetically. We have also studied the mechanism of propene epoxidation by hydrogen peroxide, which is industrially the most important reaction catalyzed by TS-1. We have assessed a number of aspects of propene epoxidation and the most important factors that govern the reaction mechanism and activation barrier, including the presence of water molecules, solvent reaction field, ex- ternal electric field and explicit porous zeolite environment.

- We performed all-atom computer simulations on nearly one hundred 6-, 8-, 10-, and 12- mer peptide fragments of protein G, and look for stable states. We simulated by replica- exchange molecular dynamics using Amber7 with the parm96 force-field and a GB/SA (generalized-Born/solvent accessible) implic- it solvent model. We find that useful diag- nostics for identifying stable converged structures are the conformational entropy and free energy of each state. A large gap in the ground-state free-energy, and a low entropy indicate convergence to a single preferred peptide conformation. We find that a non- negligible fraction of such structures have some native-like character. Such physics- based modeling may be useful for identifying early nuclei in folding kinetics and for assisting in protein-structure prediction methods that utilize the assembly of peptide fragments.

- Mur ligases represent an essential role in the biosynthesis of bacterial peptidoglycan and represent attractive targets for the design of novel antibacterials. Using protein crystallog- raphy we determined the structure of sever- al N-sulfonyl-D-Glu derivatives in complex with MurD ligase from E. coli. The series of substituted naphtalene analogues with known details of the binding mode of the inhibitors enabled also structure-activity relationships (work performed in collaboration with researchers of Lek d.d. and Faculty for Pharmacy).

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- razvili smo kvantitativne korelacije med strukturo in aktivnostjo za serijo fluorokinolonskih zaviralcev, ki so pomembni kot antiinfektivne u~inkovine.

- Predlagali smo nov fizikalni mehanizem, ki mikrovalovno katalizo razlaga na osnovi rotacijsko vzbujenih reaktivnih zvrsti, ter njegovo veljavnost potrdili s pomo~jo ra~unalni{ke simulacije realisti~ne kemijske reakcije – nevtralne hidrolize estra. Ta neravnote`ni sistem smo formalno opisali z vpeljavo rotacijske temperature, ki je vi{ja od translacijske temperature. Na nivoju teorije gostotnega funkcionala smo zgradili Born- Oppenheimerjevo povr{ino ter jo uporabili v spremenjeni Monte Carlo shemi. Kadar je rotacijska temperatura vi{ja od translacijske temperature, simulacija vodi do zni`anja aktivacijske proste energije – kataliti~nega efek- ta. Na{ izra~un tako napoveduje, da pri ro- tacijski temperaturi 310 K in translacijski temperaturi 300 K reakcija poteka 4,5–krat hitreje kot v primeru, ko sta obe temperaturi 300 K.

Ta mikrovalovni kataliti~ni efekt je manj izrazit pri vi{jih temperaturah, kar ima lahko resne posledice za interakcijo mikrovalov z `ivimi organizmi v kontekstu vseprisotne mobilne telefonije.

- Izvedli smo vrsto ab initio, DFT ter semi- empiri~nih izra~unov reaktivnosti kon~nega karcinogena akrilamida z gvaninom. Akrila- mid – produkt Maillardove reakcije – nastaja pri procesu cvrtja. Po zau`itju ga citokrom P450 2E1 epoksidira do kon~nega karcinogena – glicidamida. Efekte hidratacije smo obravnavali s pomo~jo modelov reakcijskega polja topila ter Langevinovih dipolov. In silico aktivacijske proste energije se odli~no ujemajo z eksperimentalno vrednostjo 22,8 kcal/mol.

To ujemanje potrjuje veljavnost predlaganega S_N2 reakcijskega mehanizma in ka`e na upo- rabnost kvantno-kemijskih metod pri obravnavi reakcij povezanih s karcinogenezo.

Hkrati smo napovedali neznatno stereosele- ktivnost obravnavane reakcije. Nenazadnje

- Targeted nanosecond molecular dynamics (TMD) simulations were used to obtain a dynamic model of both substrates (ATP in UDP-MurNAc-L-Ala) binding to their respective binding sites and analysis of the C-ter- minal domain closure in MurD.

- A hybrid quantum mechanical-molecular mechanical (QM/MM) modeling approach was used to study the mechanism of tetra- hedral intermediate formation which is fre- quently used as template in the design of novel inhibitors. The corresponding reaction models are in agreement with experimental reaction sequence.

- We have developed the quantitative structure activity relationships in a series of fluor- oquinolones which represent important an- tibacterias.

- We proposed a novel physical mechanism for microwave catalysis based on rotationally excited reactive species and verified its validity through a computer simulation of a realistic chemical reaction – neutral ester hydrol- ysis. This non-equilibrium system is formally described by introducing rotational temperature, which is higher than the translational temperature. A Born-Oppenheimer surface was constructed on the density functional theory level and applied to a modified Mon- te Carlo scheme. The simulation gave a re- duced activation free energy when the rotational temperature was higher than the translational temperature, which constitutes a catalytic effect. For example, our calculation predicts that with rotational and translational temperatures of 310 and 300 K, respective- ly, the reaction should proceed 4.5 times fast- er than when both temperatures are 300 K.

Moreover, this microwave catalytic effect is less pronounced at higher temperatures, which may have serious implications for the interaction of microwaves with living organ- isms in the context of widespread mobile telephony.

- We performed a series of ab initio, density

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smo simulirali konkuren~no reakcijo glicidamida z adeninom in uspe{no reproducirali eksperimentalno regioselektivnost.

- [tudirali smo interakcije 1,4-dihidropiridin- skih antagonistov (1,4-DHP), ki so antago- nisti kalcijevih L ionskih kanalov, z razli~nimi topili. DHP so v klini~ni uporabi za zdravljen- je angine pektoris, hipertenzije in drugih kar- diovaskularnih obolenj na osnovi kalcijevih L- kanalov.

- Uporabili smo volumetri~ne metode, vibracijsko spektroskopijo in kvantno kemijske izra~une.

- Dobili smo dobro ujemanje med eksperimentalnimi in izra~unanimi koli~inami. [tudija je prvi korak k realisti~nemu atomisti~nemu modeliranju inhibicije kalcijevih kanalov L tipa.

- [tudirali smo pristop simulacije H/D kineti~nih izotopskih efektov v encimski katalizi s prop- agacijo nuklearne valovne funkcije. Za primer smo vzeli kataliti~ni korak sojine lipoksi- genaze tipa 1. Kineti~ni izotopski efekt smo izra~unali kot razmerje hitrosti kemijskih reakcij za reakcijo z H in reakcijo z D. Konstante reakcijske hitrosti smo izra~unali s ~asovnega poteka nukelarnih valovnih funckij za H in D.

Propagacije smo napravili na osnovi enodi- menzionalnih protonskih potencialov z upo{tevanjem celotnega proteina. Dokazali smo, da integracija po poti predstavlja racion- alno metodologijo za izra~une kineti~nih izotopskih efektov za encimske reakcije.

- V okviru dela na podro~ju bioinformatike smo {tudirali evolucijske mehanizme v obliki zamenjav nukleotidov, vrinkov, izpustitev in zdrsov pri procesu replikacije. Proces nukle- otidnih zamenjav smo modelirali s pomo~jo minimalnega {tevila prostih parametrov. Nuk- leotidna zaporedja smo razdelili v {tiri kate- gorije: CpG otoke, Alu zaporedja, razred, ki je skupen tema dvema kategorijama in vsa ostala zaporedja. Pokazali smo, da so Alu zaporedja pogosto vklju~ena v CpG otoke, za katere je znano, da so nosilci velike ve~ine regulatornih elementov. Torej bo potrebno

functional theory (DFT), and semiempirical molecular orbital (MO) calculations concern- ing reaction between the ultimate carcino- gen of acrylamide and guanine. Acrylamide - a product of the Maillard reaction - is present in a variety of fried and oven-cooked food. After intake it is epoxidized by cyto- chrome P450 2E1 to yield the ultimate car- cinogen – glycidamide. Effects of solvation were considered using the Langevin dipoles (LD) and the solvent reaction field (SCRF) models. In silico activation free energies are in a very good agreement with the experimental value of 22.8 kcal/mol. This agreement presents strong evidence in favor of the validity of the proposed S_N2 reaction mechanism and points to the applicability of quantum chemical methods to studies of reactions associated with carcinogenesis. In addition, insignificant stereoselectivity of the studied reaction was predicted. Finally, the compet- ing reaction of glycidamide with adenine was simulated and the experimentally observed regioselectivity was successfully reproduced.

- We studied interactions of 1,4-dihydropyri- dine calcium channel antagonists (1,4-DHPs) with different solvents. DHPs have been used for many years in the treatment of angina pectoris, hypertension and other cardiovascular diseases on the basis of L-calcium ion channels. We used volumetric measurements, vibrational spectroscopy and quantum chemical calculations. A good agreement between experimental and computational results was found. This is a first step toward realistic atomistic modeling of the calcium L-type- chan- nel blocking.

- We explored the ability of using wave function propagation approaches to simulate isotope effects in enzymes, focusing on the large H/D kinetic isotope effect of soybean lipoxy- genase-1 (SLO-1). The H/D kinetic isotope effect (KIE) is calculated as the ratio of the rate constants for hydrogen and deuterium transfer. The rate constants are calculated

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ponovno ovrednotiti vlogo Alu elementov, ki veljajo nepomembne in zajedalske genom- ske komponente.

- V okviru dela na raziskovalnem programu P1- 0002 smo v letu 2008 objavili 12 originalnih znanstvenih ~lankov, vse v SCI revijah in vse v SCI revijah iz prvega kvartila.

- Razvili smo nove algoritme za primerjavo strukture povr{in proteinov in jih vgradil v spletni program, dostopen na naslovu http:/

/www.sicmm.org/probis/bin/probis.php, ki omogo~a napovedovanje proteinskih veza- vnih mest.

- V sodelovanju z National Institutes of Health, Bethesda, MD, ZDA, smo razvili http://

charmming.org, spletno stran, ki omogo~a enostavnejso pripravo vhodnih datotek za program CHARMM (Chemistry at HARvard Macromolecular Machaniscs). Posamezni programi v tem vmesniku so bili razviti na Kemijskem in{tituitu.

- Zaradi zahtev po ra~unalni{kih simulacijah vse ve~jih molekulskih sistemov smo nadaljevali raziskave na podro~ju inovativnih mre`nih topologij za povezovanje osebnih ra~u- nalnikov v gru~e in algoritme, ki izkoristijo lastnosti novih topologij. Nove gru~e omogo~ajo simulacije molekulskih sistemov, ki so preobse`ni za simulacije na posameznih ra~unalnikih ali celo majhnih gru~ah.

- Pri {tudiju molekularnih nihanj kolagena smo uporabili metode teorije gostotnih funkcionalov in metode s parametriziranimi polji sil.

Izra~unane spektre za neelasti~no sipanje nevtronov smo primerjali z objavljenimi eksperimentalnimi podatki in ugotovili, da se pri tvorbi sekundarne in terciarne strukture kolagenana najbolj signifikantno spremenijo vibracije amidnega V pasu na glicinu.

- V sodelovanju z Max Planck Institute for Pol- ymer Research, Mainz, Nem~ija and Depar- tamento Fisica Teorica de la Materia Conden- sada, Universidad Autonoma de Madrid, [panija, smo izvedli triskalno simulacijo molekularne teko~ine, v kateri smo sklopili atom-

from the time course of the H and D nuclear wave functions. The propagations are done using one-dimensional proton potentials generated as sections from the full multidi- mensional surface of the reacting system in the protein. We demonstrated that path in- tegration remains a method of choice when it comes to the quantization of nuclear motion in enzyme catalysis.

- The evolutionary mechanisms such as nucleotide replacements, insertions, deletions and replication slippages that are shaping the human genome were studied. The nucleotide replacement processes are modeled in terms of minimal number of parameters such as the transition/transversion ratio and some context dependent parameters. The variation of DNA sequences is scrutinized for the peri- od since mammalian origin and for the time since the last common ancestor to human and chimpanzee. A special emphasis is given to the distinction between four sequence categories that emerge when the genomic sequences are partitioned into i) CpG rich islands, ii) Alu - type short interspersed repeats, iii) the cross section of these two categories and iv) the class of all the remaining genomic sequences. It is shown that although the Alu sequences seem to be a typical repre- sentative of “junk DNA” they participate in CpG islands, which are known to embed the regulatory regions and are thus the sequences of supreme functional importance.

- As part of the work under the research program P1-0002 we published 12 original scientific articles, which all appear in SCI journals and all of them in the first quartile of SCI journals.

Some of the major achievements are the following:

- We have developed new algorithms for protein structure comparison and have imple- mented them into a web program accessible at http://www.sicmm.org/probis/bin/

probis.php, which enables to predict protein- protein binding sites.

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ski, mezoskopski in kontinuumski opis teko~ine. Na{ ve~skalni pristop, ki pokriva kra- jevne skale z razponom od mikro do makroskale, je kombinacija dveh dvoskalnih pristopov: del~ne AdResS in hibridne sheme HybridMD. Zdru`ena shema AdResS-Hybrid- MD uspe{no re{i problem vstavljanja velikih molekul v gosto teko~ino v hibridnih del~no- kontinuumskih simulacijah molekularnih teko~in. Zdru`ena shema odpre mo`nost iz- vajanja u~inkovitih velekanoni~nih simulacij molekulske dinamike odprtih sistemov molekularnih teko~in.

- Dr. Du{anka Jane`i~ je Associate Editor revije Journal of Chemical Information and Mode- ling (JCIM), An American Chemical Society Publications (2001 – sedaj).

- Dr. Du{anka Jane`i~ je ~lanica Editorial Board- a: Advances in Chemoinformatics and Com- putational Methods (ACCM), Book Series, IGI Global, MIT Press (2007 – sedaj).

- Dr. Milan Hodo{~ek je soavtor in razvijalec najbolj uporabljanega ra~unalni{kega progra- ma za molekularno modeliranje - CHARMM (Chemistry at HARvard Molecular Mechan- ics).

SODELOVANJE Z INDUSTRIJSKIMI IN DRU- GIMI PARTNERJI

Sodelujemo s podjetjema Krka d.d., Novo mes- to in Lek d.d., Ljubljana, na podro~ju vibracijske spektroskopije. Razvijamo nove metode, ki omogo~ajo bolj{e in nata~nej{e vrednotenje vibracijskih spektralnih parametrov. Sodelujemo pri teko~i problematiki analiznega laboratorija in tudi pri njihovih razvojnih nalogah.

S podjetjem Lek d.d., Ljubljana, enota Raziskave u~inkovin, smo sodelovali na razvoju novih u~inkovin na antiinfektivnem terapevtskem podro~ju.

Pri raziskavah, ki jih izvajamo v okviru na{ega raziskovalnega dela v Centru za molekularno modeliranje na Kemijskem in{titutu, v sodelovanju s podjetjem Lek, d.d., Ljubljana, enota Raziskave u~inkovin, delamo na projektih

- In collaboration with the National Institutes of Health, Bethesda, MD, USA we have developed http://charmming.org, a web inter- face to prepare input files for the CHARMM (Chemistry at HARvard Macromolecular Machaniscs) program. Some of the programs which run the web site were developed at the National Institute of Chemistry, Slovenia.

- Due to the increasing size of molecular systems that we wish to study with computer simulations, we have continued our research on novel network topologies for connecting personal computers into clusters as well as the algorithms that complement the new topologies. With these clusters and algorithms, computer simulations can be performed of molecular systems that are too big for simulating on individual computers or even small clusters.

- We used density functional theory methods and analytical force fields to investigate the molecular vibrations of a model collagen compound. The results were validated by comparison with published inelastic neutron scattering data. We found the strong modi- fication of Amide V vibration of glycine as the most significant vibrational signature of secondary and tertiary structure formation.

- In collaboration with the Max Planck Insti- tute for Polymer Research, Mainz, Germany and Departamento Fisica Teorica de la Mate- ria Condensada, Universidad Autonoma de Madrid, Spain, we have performed a triple- scale simulation of a molecular liquid, in which the atomistic, mesoscopic and continuum descriptions of the liquid are concur- rently coupled. This multiscale approach, which covers the length-scales ranging from the micro- to macro-scale, is a combination of two dual-scale models: a particle-based Adaptive Resolution Scheme (AdResS) and a hybrid continuum-molecular dynamics scheme (HybridMD). The combined AdResS- HybridMD scheme successfully sorts out the problem of large molecule insertion in the

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raziskav za obdelavo NMR spektrov in moleku- larnega modeliranja kot pomo~ pri interpretaciji NMR spektrov. Sodelujemo tudi z Institutom Jo`ef Stefan, Medicinsko fakulteto, Fakulteto za matematiko in fiziko, Biotehni{ko fakulteto, Fakulteto za farmacijo, Fakulteto za ra~unalni{tvo in informatiko (vse Univerza v Ljubljani) ter Primorsko univerzo, FAMNIT.

MEDNARODNO SODELOVANJE - Slovensko-hrva{ka bilaterala 2007-2008 - Slovensko-makedonska bilaterala 2007-2008 Kemijski in{titut, Center za molekularno modeliranje in RIKEN Yokohama Institute, High Per- formance Molecular Simulation Team, Japons- ka sta podpisala tri letni sporazum o znanstveno raziskovalnem sodelovanju (Collaborative Re- search Agreement) na podro~ju razvoja namen- ske strojne in programske opreme za izvajanje simulacij molekulske dinamike biolo{kih makromolekul. Na slovenski strani je odgovorna nosil- ka projekta dr. Du{anka Jane`i~, glavni izvaja- lec pa dr. Milan Hodo{~ek. Tovrstno sodelovanje potrjuje, da smo med vodilnimi svetovnimi razvijalci vzporednih ra~unalni{kih gru~ za izvajanje vzporednih simulacij molekulske dinamike velikih sistemov, ki jih uspe{no uvaja- mo v Sloveniji in s {irokim mednarodnim sodelovanjem tudi slovenskim raziskovalcem omogo~amo dostopnost do vrhunske strojne in programske opreme.

Sodelujemo pri financiranih bilateralnih projektih z raziskovalci iz naslednjih dr`av:

- z ZDA: dr. Bernard R. Brooks, National Insti- tutes of Health, Bethesda, MD

- s Hrva{ko: dr. Sonja Nikoli}, Institute Rudjer Bo{kovi}, Zagreb

- s Hrva{ko: dr. Zvonimir Maksi~, Institute Rud- jer Bo{kovi}, Zagreb

- z Romunijo: dr. Mircea Diudea, University of Cluj, Cluj

- s Poljsko: dr. Aleksander Koll, University of

hybrid particle-continuum simulations of molecular liquids. The combined model, which correctly describes the hydrodynam- ics within the hybrid particle-continuum framework, opens up the possibility to per- form efficient grand-canonical molecular dynamics simulations of truly open molecular liquid systems.

- Dr. Du{anka Jane`i~ is the Associate Editor of the Journal of Chemical Information and Modeling (JCIM), An American Chemical So- ciety Publications (2001 – present).

- Dr. Du{anka Jane`i~ is a member of the Edi- torial Board: Advances in Chemoinformatics and Computational Methods (ACCM), Book Series, IGI Global, MIT Press (2007 – present).

- Dr. Milan Hodo{~ek is a coauthor and devel- oper of the widely used computer program for molecular modeling – CHARMM (Chem- istry at HARvard Molecular Mechanics).

COLLABORATION WITH INDUSTRIAL AND OTHER PARTNERS

- We cooperate with pharmaceutical compa- nies Lek d.d., Ljubljana, Slovenia, and Krka d.d., Slovenia. We developed the quantitative methods for determination of drug crystallinity using Raman and FTIR spectroscopy.

We developed a new method suitable for rapid and accurate determination of various types of drug crystallinity. The method is based on the modified PCR analysis of Ram- an spectra. The rapid quantitative feed back information about the type of drug crystallinity enables efficient change of the crystal- lization parameter to rationalize drug pro- duction.

- In collaboration with Lek d.d., Ljubljana, Slov- enia, Drug Discovery we develop novel chemical entities (NCE’s) in the antiinfective and cardiovascular therapeutic areas and we also collaborate on research projects for process- ing NMR spectra using molecular modeling approaches.

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Wroclav, Wroclav

- z Rusijo: dr. Vladimir Poroikov, Institute of Biomedical Chemistry of Russian Academy of Medical Sciences, Moscow

- s Francijo: dr. Mark Johnson, ILL, Grenoble POMEMBNI IN[TRUMENTI IN OPREMA - Izgradili smo vzporedni ra~unalniski sistem

VRANA-12

- FTIR spektrometer Perkin Elmer sistem 2000 z NIR Raman spektrometrom

- FTIR Bruker 66 S - Suha komora Braun - Diamantna ATR celica IZOBRA@EVANJE IN OBISKI / GOSTOVANJA

- Dr. Matej Praprotnik je bil habilitiran v do- centa za podro~je fizike na Fakulteti za matematiko in fiziko, Univerza v Lubljani - Mladi raziskovalec Janez Konc (mentorica dr.

Du{anka Jane`i~) je pridobil naslov doktorja znanosti na Fakulteti za farmacijo, Univerza v Lubljani

- Mlademu raziskovalcu Nejcu Carlu (mentorica dr. Du{anka Jane`i~) je bil odobren direktni prehod na doktorski {tudij na Fakulteti za kemijo in kemijsko tehnologijo, Univerza v Lubljani

- Mladi raziskovalki Gordani Pirc (mentor prof.

dr. Branko Bor{tnik) je bil odobren direktni prehod na doktorski {tudij na Fakulteti za kemijo in kemijsko tehnologijo, Univerza v Lubljani

- Bla` Vehar je diplomiral na Fakulteti za farmacijo, Univerza v Lubljani, (somentorica dr.

Du{anka Jane`i~)

- Dr. Urban Bren je v zimskem semestru {tud- ijskega leta 2008/2009 kot gostujo~i docent predaval predmet Physical Chemistry I dodiplomskim {tudentom kemije in foren- zi~nih znanosti na Department of Chemis- try, Loyola University Chicago, ZDA

- We collaborate with Jo`ef Stefan Institute, Slovenia; Faculty of Medicine, Faculty of Mathematics and Physics, Biotechnical Fac- ulty, Faculty of Pharmacy, Faculty of computer and information science (all University of Ljubljana, Slovenia). We also collaborate with the University of Primorska, FAMNIT.

INTERNATIONAL COLLABORATION - Slovenia-Croatia bilateral project 2007-2008 - Slovenia-Macedonia bilateral project 2007-

2008

The National Institute of Chemistry, Center for Molecular Modeling and the RIKEN Yokohama Institute, High Performance Molecular Simula- tion Team, Japan have signed a three year collaborative research agreement on computer hardware and molecular dynamics simulation methods development. The principal investiga- tor in Slovenia is Dr. Du{anka Jane`i~ and the main personnel in Slovenia is Dr. Milan Hodo{~ek. Such collaboration proves that we are among leading developers of parallel computer clusters to be used for molecular dynamics simulations of large systems, which we successfully introduced to Slovenia.

We collaborate on financed bilateral projects with researchers from the following countries:

- USA: Dr. Bernard R. Brooks, National Insti- tutes of Health, Bethesda, MD

- Croatia: Dr. Sonja Nikoli}, Institute Rudjer Bo{kovi}, Zagreb

- Croatia: Dr. Sanja Tomi}, Institute Rudjer Bo{kovi}, Zagreb

- Romania: Dr. Mircea Diudea, University of Cluj, Cluj

- France: Proteus project, Prof. Dr. Mark John- son, Institute Laue Langevin, Grenoble - Poland: Dr. Aleksander Koll, University of

Wroclav, Wroclav

- Russia: Dr. Vladimir Poroikov, Institute of Bi- omedical Chemistry of Russian Academy of Medical Sciences, Moscow