engleski

Force field based methods for computational study of macromolecules

Revealing of the life secrets requires a complex approach to biological problems utilizing both the experimental and the theoretical methods. Recognition between biologically important molecules is a result of balance between different molecular properties: shape, charge distribution, entropy and dynamics. In order to investigate the molecular properties and correlate the structural parameters with biological activity we use various molecular modelling methods in our research, as well as statistical and data processing approaches. However, these investigations depend on the existence of the reliable 3D structure of macromolecules. For this purpose the X-ray diffraction is the most widely used methods. Follow neutron diffraction, NMR, microscopic and spectroscopic methods. Development of computers, their relatively low price and plethora of available software resulted in wide application of molecular modelling in almost all biosciences. In the lecture I'll explain difference between quantum mechanical and empirical methods and outline a general procedure that could be used in study of proteins and their complexes. The most often used techniques of molecular modelling will be outlined: protein homology modelling, geometry optimisation, building 3D structure of small molecules, ligand docking, protein flexibility investigation by molecular dynamics (MD) simulations and Normal modes analysis (NMA). Also I'll explain the basic idea of hybrid, QM/MM method and its applicability in modelling enzymatic reactions. Finally, I'll give a possible scenario for modelling a virtual (in silico) experiment and how to use it as a template for the true one. For this purpose the main idea of 3D-QSAR (3-dimensional quantitative structure activity relationship) analysis will be explained, as well as importance of skill in models interpretation, predicting biological response and finding the modification that would change this response.

molecular modeling; proteins

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