Ligand binding effect on protein vibrational dynamics and its implications for drug design

Abstract:

New elastic network modeling approaches will be presented for analyzing conformational dynamics of large protein complexes. Experimental verification based on a large dataset indicates correlations above 0.9 after incorporation of small ligands at atomistic detail. For most proteins, the vibrational frequency spectrum narrows down due to interactions with ligands. In this respect, changes in the functional modes of motion can be quantified due to binding of allosteric or orthosteric ligands. Such approaches may be efficiently utilized in drug design studies for conformational sampling of flexible proteins and for determining the docking poses that affect enzyme’s functional dynamics.