A quantitative measure of conformational changes in Apo, holo and ligand bound form of enzymes.

Abstract

Determination of the native geometry of the enzymes and ligand complexe is a key step in the process of structure based drug designing. Enzymes and ligands show flexibility in structural behavior as they come in contact with each other. When ligand binds with active site of the enzyme, in presence of cofactor some structural changes are expected to occur in the active site. Motivation behind this study is to determine the nature of conformational changes as well as regions where such changes are more pronounced. To measure the structural changes due to cofactor and ligand complex, enzyme in Apo, holo and ligand bound form is selected. Enzyme data set was retrieved from protein data bank (PDB). 15 triplet groups were selected for the analysis of structural changes based on selection criteria. Structural features for selected enzymes were compared at the global as well as local region. Accessible surface area for the enzymes in entire triplet set was calculated, which describes the change in accessible surface area upon binding of cofactor and ligand with the enzyme. It was observed that some structural changes take place during binding of ligand in presence of cofactor. This study will helps in understanding the level of flexibility in protein-ligand interaction for computer aided drug designing.