BEGIN:VCALENDAR VERSION:2.0 PRODID:-//CERN//INDICO//EN BEGIN:VEVENT SUMMARY:In the search of the HDAC-1 inhibitors. The preliminary results of ligand based virtual screening. DTSTART;VALUE=DATE-TIME:20121019T120000Z DTEND;VALUE=DATE-TIME:20121019T123000Z DTSTAMP;VALUE=DATE-TIME:20261011T051825Z UID:indico-contribution-90-160@indico.ipb.ac.rs DESCRIPTION:Speakers: Cvijetić Ilija N. (Innovation Center of the Faculty of Chemistry\, University of Belgrade\, Studentski Trg 12-16\, Belgrade)\ nAcetylation and deacetylation of histone is an important mechanism to reg ulate the DNA expression. Two main classes of enzymes catalyze this regula tory mechanism: histone acetyltransferase (HAT) and histone deacetylase (H DAC). HDACs are involved in signal transduction\, cell growth and cancer [ 1]. We report the results of the preliminary ligand-based virtual screenin g in the search of the novel HDAC-1 inhibitors. By this virtual screening study\, we aimed to test the performances of the OpenEye applications inst alled on our home cluster PARADOX. As the template\, we used the ligand fr om 3MAX PDB entry [2]\, Figure 1. (HDAC-2 isozyme has the identical active site with HDAC-1). The ChemBank set of 2346 molecules was taken from the ligand.info [3]. After the filtering (exclusion of the metal containing co mpounds\, and limiting of the number of HBA (10) and HBD (5)) we obtained 1990 molecules\, which are submitted to OMEGA [4] to generate conformation al assemblies of the molecules studied. The OMEGA options were set to defa ult\, yielding ~ 142000 conformers in total. We searched the shape and the pharmacophoric similarity of the multiconformer ligand set against the te mplate molecule by ROCS program [5]. The best-ranked solution of the 100 h its by TanimotoCombo score (1.305) was Nifenazone\, that has been used as the analgesic drug and was withdrawn due to heavy side effects. The subset of ligand conformers prepared with ROCS is further submitted to EON [6]\, to search for the electrostatic similarity to the template molecule. The compound labeled as the itdac-7 in ChemBank appears as the best-ranked sol ution by the ET-combo score (1.403)\, Figure 1b. There is no literature da ta on this compound\, but ChemBank results from the high-throughput screen ing campaigns indicates itdac-7 as active toward enzymes involved in deace tylation. Our preliminary screen\, as reported in this communication\, inv olves the MMFF94s charges ascribed by default. Further work will be direct ed to assignation of the semiempirical charges for the electrostatic simil arity screen\, using the larger database of the compounds. All calculation s by OpenEye applications were performed in BJD work group on PARADOX clus ter\, Institute of Physics\, Belgrade.\nAcknowledgement: The work reported makes use of results produced by the High-Performance Computing Infrastru cture for South East Europe’s Research Communities (HP-SEE)\, a project co-funded by the European Commission (under Contract Number 261499) throug h the Seventh Framework Programme HP-SEE (http://www.hp-see.eu/).\nThe Min istry of Education and Science of Serbia support this work. Grant 172035. \nReferences: [1] Nature 389 (1997) 349\; [2] Bioorg. Med. Chem. Lett. 20 (2010) 3142\; [3] Comb. Chem. High. Throughput Screen. 7 (2004) 757\; [4] J. Chem. Inf. Model. 50 (2010) 572\, OMEGA 2.4.2\; [5] J. Med. Chem. 48 (2 005) 1489\, ROCS 3.1.1\; [6] EON 2.0.1\, OpenEye Scientific Software\, In c.\, Santa Fe\, NM\, USA\, www.eyesopen.com .\n\nhttps://events.saifa.rs/e vent/291/contributions/160/ LOCATION:National Library of Serbia URL:https://events.saifa.rs/event/291/contributions/160/ END:VEVENT BEGIN:VEVENT SUMMARY:Investigations of biomolecular systems within the ISyMAB simulatio n framework DTSTART;VALUE=DATE-TIME:20121019T113000Z DTEND;VALUE=DATE-TIME:20121019T120000Z DTSTAMP;VALUE=DATE-TIME:20261011T051825Z UID:indico-contribution-90-163@indico.ipb.ac.rs DESCRIPTION:Speakers: Ionut Vasile (IFIN-HH)\nISyMAB is an integrated fram ework that provides secured access to a distributed set of molecular dynam ics tools for modeling and simulation of large bio-systems using high-perf ormance computing. It relies upon open-source software (such as NAMD\, MMT SB tool set\, VMD) and in-house developed analysis scripts\, which are mad e available through a\nuser-friendly graphical interface.\n\nISyMAB brings a significant contribution to the optimization of the creation of the fil es needed by the job management system and the simulation description file s. Also\, it minimizes the time between successive runs\, making the nodes within the HPC clusters run with maximum efficiency.\n\nThe use and the p erformances of the framework is illustrated through the molecular dynamics study of an acid-sensing ion channel in a 200x200 Angstrom lipid bilayer simulated within a 800 000 atoms system.\n\nhttps://events.saifa.rs/event/ 291/contributions/163/ LOCATION:National Library of Serbia URL:https://events.saifa.rs/event/291/contributions/163/ END:VEVENT BEGIN:VEVENT SUMMARY:Design of novel nano-photonic materials DTSTART;VALUE=DATE-TIME:20121019T100000Z DTEND;VALUE=DATE-TIME:20121019T103000Z DTSTAMP;VALUE=DATE-TIME:20261011T051825Z UID:indico-contribution-90-174@indico.ipb.ac.rs DESCRIPTION:Speakers: Manthos Papadopoulos (National Hellenic Research Fou ndation)\nDesign of novel nano-photonic materials\n\n\nManthos G. Papadopo ulos*\, Aggelos Avramopoulos\n\nInstitute of Biology\, Medicinal Chemistry and Biotechnology\, National Hellenic Research Foundation\, 48 Vas. Const antinou Ave.\, Athens 116 35\, Greece\n*E-mail: mpapad@eie.gr\n\n\n We have designed or selected a series of derivatives\, which have very high linear and nonlinear optical L&(NLO) properties and which are likely to be useful for photonic applications. The compounds belong to three families : \n(a) Noble gas derivatives. These involve one or more noble gas (Ng) atoms inserted in the chemical bond A-B [1-2]. We have considered a numbe r of such derivatives\, for example HArF\, HXeC2H. It has been found that\ , in general\, the inserted noble gas atom increases remarkably the NLO p roperties. Two novel Xe derivatives have also been proposed: HXeOXeF and F XeOXeF. Their electronic ground state\, the stability and their L&NLO prop erties have been studied [2]. \n(b) Ni-dithiolene derivatives. We discuss how the diradicaloid character (DC) of Ni(SCH)4\, which is used as model d erivative\, affects the L&NLO properties. It has been found that the quasi degeneracy of the two lowest-energy singlet states\, 1 1Ag and 1 1B1u\, th e clear DC nature of the former and the very large number of low-lying sta tes increase the NLO properties. The very large effect of Ni on the proper ties of interest is demonstrated. A series of Ni-dithiolene derivatives w ith very large NLO properties are proposed [3].\n(c) Fullerenes. Using a w ide variety of quantum-chemical methods we have analyzed in detail the L&N LO properties of [60]fullerene-chromophore dyads of different electron-don or character [4]. The dyads are composed of [60]fullerene covalently linke d with 2\,1\,3-benzothiadiazole and carbazole derivatives. Substitution o f 2\,1\,3-benzothiadiazole by the triphenylamine group significantly incr eases the electronic first and second hyperpolarizabilities. \n These studies have been performed by employing a series of methods: HF\, DFT\, MP2\, MS-CASPT2\, CCSD and CCSD(T). \n\n1. A.Avramopoulos\, H. Reis\, J . Li and M. G. Papadopoulos\, J. Am. Chem. Soc.\, 126\, 6179 (2004)\; F. Holka\, A. Avramopoulos\, O. Loboda\, V. Kellöand M. G. Papadopou los\, Chem Phys. Letters\, 472\, 185 (2009)\; A. Avramopoulos\, L. Serrano-Andrés\, J. Li\, M. G. Papadopoulos\, J. Chem. Theor. Comp.\, 6\ , 3365 (2010)\; A. Avramopoulos\, Luis-Serrano-Andrés\, H. Reis\, M. G.Papadopoulos\, J. Chem. Phys.\, 127\, 214102 (2007).\n2. A. Avram opoulos\, J. Li\, N. Holzmann\, G. Frenking\, M. G. Papadopoulos\, J. Phys. Chem. A\, 115\, 10226 (2011).\n3. L. Serrano-Andrés\, A. Avramop oulos\, J. Li\, P. Labéquerie\, D. Bégué\, V. Kellö\, and M. G. Pa padopoulos\, J. Chem. Phys\,. 131\, 134312 (2009). \n4. O. Loboda\, R. Zalesny\, A. Avramopoulos\, J. M. Luis\, B. Kirtman\, N. Tagmatarch is\, H. Reis\, M. G. Papadopoulos\, J. Phys. Chem. A\, 113\, 1159 (200 9).\n\nhttps://events.saifa.rs/event/291/contributions/174/ LOCATION:National Library of Serbia URL:https://events.saifa.rs/event/291/contributions/174/ END:VEVENT BEGIN:VEVENT SUMMARY:Free-energy surfaces of 2-[(carboxymethyl)sulfanyl]-4-oxo-4-arylbu tanoic acids. Molecular dynamics study in explicit solvents. DTSTART;VALUE=DATE-TIME:20121019T110000Z DTEND;VALUE=DATE-TIME:20121019T113000Z DTSTAMP;VALUE=DATE-TIME:20261011T051825Z UID:indico-contribution-90-191@indico.ipb.ac.rs DESCRIPTION:Speakers: Branko Drakulic (Department of Chemistry-IChTM\, Uni versity of Belgrade)\nThe 2-[(carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids (Scheme 1) exert antiproliferative potency and significant selectiv ity toward human tumor cells in vitro in low micromolar to submicromolar c oncentrations [1]. In the congeneric set of compounds we observed the regu larity between the selectivity and the properties derived from the conform ational assemblies of compounds [2]. As the part of ongoing studies\, in t his communication we repot the free-energy surfaces of the representative congeners (some examples is given on the Figure 1)\, as obtained by molecu lar dynamics simulations\, using adaptive biasing force (ABF) procedure [3 ] to speed-up sampling of the systems. All simulations were performed invo lving simulation of explicit solvents having different polarity and hydrog en bond donor/acceptor abilities (water\, chloroform\, dimethyl-sulfoxide\ , ethanol\, n-octanol/water mixture)\, lasting from 20 to 50 ns. For compa rison\, the molecular dynamics simulations on the representative system wi thout applied biasing forces was also reported. The differences in the fre e-energy surfaces of the same\, representative\, congener in different sol vents reflect the fact that flexible molecules change conformations in a w ay to mimic surroundings (i.e. solvent in which are dissolved) [4]. Range s of property spaces [5] of compounds under the study were analyzed and co mpared. In all simulations molecules were treated in their neutral form. T he effect of using different types of atomic charges on the final results is also commented. All systems under the study were minimized during 20000 steps\, than heated to 310 K for 10000 steps. Molecular dynamics simulati on\, on 310 ± 10 K\, with applied ABF procedure was performed on the each system. CHARMm22 force field and Geisteiger charges\, or charges derived from the semiempirical calculations\, were used. Electrostatics was treate d by Particle Mesh Ewald method. The periodic boundary conditions were app lied\, and 12 Å cut-off (8 Å switching)\, with pair list distances set t o 13.5 Å. All calculations were performed by NAMD 2.8 [6] on the multimod e Linux cluster. For the preparation of the systems and analysis of the re sults VegaZZ 2.4.0 was used [7].\n\n\nAcknowledgement: The work is support ed by the European Commission under EU FP7 project HP-SEE\, http://www.hp- see.eu/. The Ministry of Education and Science of Serbia support this work . Grant 172035. \n\n\nReferences: [1] J. Med. Chem. 48 (2005) 5600\; [2] a ) The 18th European Symposium on Quantitative Structure-Activity Relations hips\, Book of Abstracts\, pp. 278-279\, Greece\, 2010\; b) The 19th Europ ean Symposium on Quantitative Structure-Activity Relationships\, Book of A bstracts\, p 147\, Austria\, 2012\; [3] J. Chem. Theory Comput. 6 (2010) 3 5\; [4] Med. Res. Rev. 17 (1997) 303\; [5] J. Med. Chem. 48 (2005) 4947\; [6] J. Compt. Chem. 26 (2005) 1781\; [7] J. Comp. Aided Mol. Des. 18 (2004 ) 167\n\nhttps://events.saifa.rs/event/291/contributions/191/ LOCATION:National Library of Serbia URL:https://events.saifa.rs/event/291/contributions/191/ END:VEVENT BEGIN:VEVENT SUMMARY:Efficient Parallel Simulations of Large-Ring Cyclodextrins on HPC cluster DTSTART;VALUE=DATE-TIME:20121019T103000Z DTEND;VALUE=DATE-TIME:20121019T110000Z DTSTAMP;VALUE=DATE-TIME:20261011T051825Z UID:indico-contribution-90-195@indico.ipb.ac.rs DESCRIPTION:Speakers: Emanouil Atanassov (Institute of Information and Com munication Technologies\, Bulgarian Academy of Sciences)\nA new class of c ompounds\, the large-ring cyclodextrins (LR-CDs)\, attracted attention in recent years\, and advances were marked in the study of their physicochemi cal properties in spite of existing difficulties in their synthesis\, isol ation and purification. Practical applications were also reported of this new class of compounds. Understanding the mechanism of their action requir es knowledge of the macroring conformational dynamics. In view of the diff iculties with the experimental examination of the conformations of LR-CDs\ , computational modeling and simulation methods provide useful tool to gai n information about their conformational dynamics\, the energetics\, and t he complex-forming ability.\nUsing molecular dynamics simulations as a con formational search protocol\, post-processing of the simulation trajectori es is carried out by: (i) the MM/GBSA (Generalized Born/Surface Area (LCPO )) methodology in order to estimate energy data\, and (ii) principal compo nent analysis (PCA)\, also called quasiharmonic analysis or essential dyna mics method. With the methodology used we can monitor the concerted motion s of the atoms of the molecule in a few dimensions\, making it easier to v isualize and investigate these motions. After examining the conformational interconversions in some lower-size LR-CDs (CDn\, n=10\, 11\, …\, 30)\, 1-3 our efforts are focused now on treating problems with much higher dime nsionality\, e.g. CD100\, as well as on inclusion complexes of LR-CDs. Due to the access to more powerful computational resources and parallelized s oftware it became practically feasible to execute molecular dynamics confo rmational searches with longer duration for large cyclodextrins examined b y us earlier with very short simulations\, 5.0 ns (CDn\, n=40\, 55\, 70\, 85\, 100\; Giant cyclodextrins).4\nSuch studies require enormous computati onal resources and it is of crucial importance to make the proper choice o f optimal hardware\, as well as software configurations in order to execut e the computations efficiently. We present in this report results produced at the HPC cluster at IICT-BAS with Infiniband interconnection\, which is part of the HP-SEE infrastructure. All tests are in support for optimal e xecution of the specifically parallelized module PMEMD of AMBER v.11 with 64 cores on eight nodes. \n___________________\n1 M. Gotsev\, P. Ivanov\, J. Phys. Chem. B\, 2009\, 113\, 5752-5759.\n2 P. Ivanov\, J. Phys. Chem. B\, 2010\, 114\, 2650-2659. \n3 P. Ivanov\, In: Current Physical Chemist ry: Biomolecular Simulations and Applications\, Vol. 2\, 2012\, in press.\ n4 P. Ivanov\, C. Jaime\, J. Phys. Chem. B\, 2004\, 108\, 6261-6274.\n\nht tps://events.saifa.rs/event/291/contributions/195/ LOCATION:National Library of Serbia URL:https://events.saifa.rs/event/291/contributions/195/ END:VEVENT END:VCALENDAR