ABSTRACT
The searching for new chemical compounds possessing specific biological activity is a complex problem that needs the usage of modern methods of molecular modeling. In particular, for the prupose of searching for potentially active compounds for whole class of SH2 domains, a comparison of all available structures, their cluster analysis, molecu- lar docking, selection of all possible pharmacophore models and GTM prediction were done. Obtained results testify to the considerable variability of binding of SH2 domains.
Subject(s)
Molecular Docking Simulation , Small Molecule Libraries/chemistry , src Homology Domains , src-Family Kinases/chemistry , Animals , Databases, Chemical , Drug Discovery , Humans , Molecular Dynamics Simulation , Thermodynamics , src-Family Kinases/antagonists & inhibitorsABSTRACT
The conformational changes of proteins play an important role in biological functioning such as ligand-protein and protein-protein interactions. The aim of the work was to investigate the conformational movement of most represented SH2 domains. It was found that SH2 domain binding pocket includes both flexible and not flexible regions: the central area of the binding pocket is the most unflexible, whereas the pTyr-binding and hydrophobic zones are the most flexible. Results of the computer analysis revealed new conformational properties of SH2 domain, which are important for drug design.