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Computational Chemistry

Prof. RNDr. Jaroslav Koča, DrSc.
Research Group Leader

THEMATIC RESEARCH FOCUS

RESEARCH AREAS

  • Structure and dynamics of proteins, nucleic acids, saccharides, and their complexes
  • Enzymatic reactions
  • Chemoinformatics and bioinformatics
  • Structure and dynamics of supramolecular complexes

MAIN OBJECTIVES

  • To study the therapeutical and bioanalytical aspects of recognition and adhesion phenomena in hostpathogen interactions.
  • To develop new methodologies for investigating the structure, interactions, and dynamics of biomolecules.

CONTENT OF RESEARCH

During the last two decades, computational chemistry has become an indispensable method that cannot be omitted from the basic tools of modern structural biology. The key feature is to describe, understand and predict the behaviour of a biomolecular system is free energy, which is especially important for understanding such phenomena as chemical equilibrium and/or kinetics. Since free energy calculations suff er from two major problems, the sampling problem and the choice of the correct reaction coordinate, we strive to develop new methods and strategies for obtaining more accurate free energies in a reasonable time. Having at hand better methods for free energy calculation, we will further continue with the development of the TRITON programme. The program has been under development in our laboratory for more than 10 years and, to the best of our knowledge, it is still very robust and reliable software for in silico protein engineering in comparisons with similar software. The TRITON programme will be tuned to allow the designing of proteins with predefined binding properties.

Free energy calculations, or molecular dynamic simulations, often critically depend on the adequacy of the molecular mechanical force fi elds and other methods describing the relation between molecular structures and energies. Therefore, much eff ort will be devoted to the development and verifi cation of these methods. This will mainly be done in the fi eld of nucleic acids, where the main attention will be paid to noncanonical architectures such as hairpin loops, which are notoriously diffi cult to describe by the force fields.

Nowadays, a large amount of information about biomolecules (i.e. sequence of DNA, structure of proteins) and about small molecules (drug-like molecules, ligands, etc.) is available. More and more structures are being solved every year thanks to the advances and increased availability of experimental techniques. The main goal of bioinformatics and chemoinformatics research is the processing of this data, which can provide useful information in pharmacy, medicine, biotechnology etc. Our laboratory is focusing on advanced analyses of protein 3D structures (searching of tunnels in proteins, charge calculations, superimposition of multiple protein motifs), processing data from next-generation sequencing and predicting of physico-chemical properties of organic molecules (QSPR modeling). We are also developing sophisticated software tools for these topics (programs Mole, EEM Solver and SiteBinder). We will further improve our approaches and apply them to biochemically important targets.

KEY RESEARCH EQUIPMENT

CURRENT RESEARCH INFRASTRUCTURE

The group operates with the research infrastructure, which is composed of computational clusters with more than 400 processors and the possibility of sharing the National Academic Supercomputer Centre resources.

MAIN PROJECTS

  • Evaluation of the binding between cerebrosterol and amyloid beta peptide 1-40 (GA305/09/0457), Czech Science Foundation, 2009-2011, Z. Krištofikova, Prague Psychiatric Center, V. Kopecky, Charles University in Prague, J. Koča, Masaryk University.
  • Research of acetylcholinesterase reactivation by methods of computation chemistry (OVMASUN200901), Ministry of Defense, 2009-2012, J. Koča, Masaryk University.
  • Molecular and structural biology of selected antitumor drugs.cytostatics. From mechanistic studies to chemotheraphy of tumors (GD301/09/H004), Czech Science Foundation, 2009-2012, V. Brabec, Institute of Biophysics AS CR, J. Koča, Masaryk University, J. Kašparkova, Palacky University Olomouc.
  • Program developing interdisciplinary research POtential for the STudies of BIOMolecular Interactions (POSTBIOMIN) (205872), FP7-CAPACITIES, EU, 2008-2011, J. Koča, Masaryk University.
  • InterBioNet – Support of the International and intersectoral R&D Co-operation in the Field of Life Sciences (CZ.1.07/2.4.00/17.0042), Ministry of Education, Youth and Sports, 2011-2014, J. Koča, Masaryk University.

SELECTED PUBLICATIONS

  • KOZMON, S., MATUSKA, R., SPIWOK, V., KOCA, J. Three-Dimensional Potential Energy Surface of Selected Carbohydrates’ CH/pi Dispersion Interactions Calculated by High-Level Quantum Mechanical Methods. Chem. Eur. J. 2011, 17(20), p. 5680-5690.
  • WIMMEROVA, M., MISHRA, N., POKORNA, M., KOCA, J. Importance of oligomerisation on Pseudomonas aeruginosa Lectin-II binding affinity. In silico and in vitro mutagenesis. J. Mol. Model. 2009, 15(6), p. 673-679.
  • ADAM, J., KRIZ, Z., PROKOP, M., WIMMEROVA, M., KOCA, J. In Silico Mutagenesis and Docking Studies of Pseudomonas aeruginosa PA-IIL Lectin – Predicting Binding Modes and Energies. J. Chem. Inf. Model. 2008, 48(11), p. 2234-2242.
  • MISHRA, N., KULHANEK, P., SNAJDROVA, L., PETREK, M., IMBERTY, A., KOCA, J. Molecular dynamics study of Pseudomonas aeruginosa lectin-II complexed with monosaccharides. PROTEINS. 2008, 72(1), p. 382-392.
  • OTYEPKA, M., BARTOVA, I., KRIZ, Z., KOCA, J. Diff erent mechanisms of CDK5 and CDK2 activation as revealed by CDK5/p25 and CDK2/cyclin A dynamics. J. Biol. Chem. 2006, 281(11), p. 7271-7281.
 

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