EFFICIENCY OF A HIERARCHICAL DOCKING PROTOCOL FOR COMPUTATIONAL LIGAND SCREENING AGAINST HOMOLOGY MODELS

Abstract

We assessed the efficiency of a hierarchical docking protocol against homology models in virtual ligand screening (VLS) studies. A low resolution model of factor X (FX) was built on a template of Trypsin molecule (PDB ID:1EB2). Afterward VLS was performed involving a hierarchical protocol, rigid body followed by flexible docking, both against model as well as an X-ray structure of FX (PDB ID:1FJS) using a smart library of 50,000 chemical compounds seeded with 9 known inhibitors of FX. The percentage enrichments of screened chemical compounds obtained both from the crystal structure and homology model of FX were compared to analyze the efficiency of the protocol. In the first 5% of the finally ranked database of the screened compounds, both against model and the X-ray structure, 67% of the inhibitors were retrieved.