Computational Chemistry Group prof. RNDr. JaroslavKoča, DrSc.
Computational chemistry experiment computational chemistry “resolution” “accuracy” Computational chemistry can complement experimental results by computer simulations of studied systems withatomic resolutionand thus provide more compact picture about studied phenomena. theory
Whowe are … Mgr. Zdeněk Kříž, Ph.D. E-mail: zdenek.kriz@ceitec.muni.cz Expertise: QM, MD, Docking RNDr. Petr Kulhánek, Ph.D. E-mail: petr.kulhanek@ceitec.muni.cz Expertise: QM, QM/MM, MD, Free Energy prof. RNDr. Jaroslav Koča, DrSc. (head) Mgr. Martin Prokop, Ph.D. E-mail: martin.prokop@ceitec.muni.cz Expertise:Software dev, Dockig • 1 professor • 5 research assistants • 1 post-doc student • 11 graduate students • 7 undergraduate students RNDr. Radka Svobodová, Ph.D. E-mail: radka.svobodova@ceitec.muni.cz Expertise:Chemo and Bioinformatics RNDr. Robert Vácha, Ph.D. E-mail: robert.vacha@ceitec.muni.cz Expertise:MD, MC, Coarse Grain, Free Energy Mgr. Stanislav Kozmon, Ph.D. E-mail: stano@chemi.muni.cz Expertise: QM, QM/MM
What we can offer … enzymes large biomolecular complexes small complexes lectins • experts in the area of computational chemistry methods molecular dynamics simulations, docking, chemo and bioinformatics, binding free energy calculation, quantum mechanics calculations, coarse grained modeling, etc. • robust computational chemistry software in silico design, free energy calculations, fast atomic charge prediction, high throughput virtual screening, prediction of protein tunnels and cavities, etc. • expertise for studying systems of various size …
Quantum mechanics (QM) • Very precise interaction energies • Reaction mechanisms Methods: semiempirical, DFT, abinito, CCSD(T) Software: gaussian, turbomole, adf, jaguar, dft-b, cpmd, mopac bambus[6]uril/anion interaction probing CH-p dispersion interaction
Hybrid QM/MM • It allows to study larger systems • Mostly reaction mechanisms • Studied systems: nucleases, glycosyltransferases Methods: semiempirical, DFT Software: cpmd + PMFLib, sander + PMFLib, adf
Conformational Space Search • Conformational changes are important processes occurring in biomolecular systems opening of free BsoBI endonuclease • Our goal is to effectivelysearch very large conformational space grid-CICADA
Molecular Dynamics • Dynamics of studied systems • Interaction with explicit solvent • Free energy of conformational changes (both reaction and activation) • Binding free energies (alchemical transformation TI, MM/PB(GB)SA) • Ions transport Methods: molecular mechanics (GAFF, PARM99SBBSC0) Software: Amber + PMFLib, Q package solvent pattern around cucurbituril b-amyloid / cerebrosterol interaction
Coarse Grained Models Access lager systems and timescales Reduce unimportant degrees of freedom Physical model
Coarse Grained Models • Self-assembly of peptides, proteins, and functionalized nanoparticles • Peptides interacting with phospholipid membrane and surfaces
Chemoinformatics • Prediction of physicochemical properties (e.g., pKa) • Development, parameterization and validation of QSAR/QSPR models • Fast calculation of empirical charges (method EEM) • QM calculation of charges (Mulliken, NPA, ESP, RESP, Löwdin) • Usage of charges as descriptors in QSAR/QSPR models • Automation of QSAR/QSPR modeling process (software QSPR Designer)
Bioinformatics Fast calculation of empirical charges in proteins (method EEM) Searching for tunnels in proteins (software Mole) Superimposition of protein motifs (software SiteBinder) Searching for protein motifs (i.e., metal and sugar binding sites) Validation of sugar denotations in PDB
Virtual Screening Motivation Target • Lectin PA-IIL Software tools Performance • AutodockVina • heterogeneous computational resources • single docking ca 1-10 minutes/ligand • ca 900 concurrently running jobs • docking speedabout 250000 ligands per day
Developed Software Triton Mole SiteBinder EEM PMFLib is a set of various programs and libraries suited for free energy calculations. It implements: adaptive biasing method, constrained dynamics, metadynamics, and others. The program TRITON is a graphical tool for computational aided protein engineering. More at: https://lcc.ncbr.muni.cz
Hardware • We have expertise in utilizations of heterogeneous computational resources: • MetaCentrum • National grid project • ca 2000 CPU cores • CEITEC/NCBR resources ca 850 CPU cores • http://metavo.metacentrum.cz/ • VOCE • European grid project • ca 8000 CPU cores • 120 TB disk space • http://egee.cesnet.cz/en/voce/ • Stereoprojections • Computer room 1.18/A4 (22+1 glasses) • Seminar room 2.11/A4 (22 glasses)
Contact prof. RNDr. JaroslavKoča, DrSc. e-mail: jaroslav.koca@ceitec.muni.cz url: http://lcc.ncbr.muni.cz Building A4, University Campus Bohunice Kamenice753/5 625 00 Brno
Thankyouforyourattention CentralEuropean Institute of Technology c/o Masarykova univerzita Žerotínovo nám. 9 601 77 Brno, CzechRepublic www.ceitec.eu | info@ceitec.cz
