Abstract

VALIDATION OF THE SCORING FUNCTION RUN IN AUTODOCK-4, A SOFTWARE USED FOR MOLECULAR DOCKING

*Punam N. Dharpure, Mohd. Shoeb and Priti S. Bhoyar

ABSTRACT

Molecular docking is the in-silico technique mostly used nowadays to screen out the drugs for the treatment of many diseases. In this study the validation of the scoring function i.e. Force field used in software used for molecular docking is done. Autodock 4 software is used for molecular docking. Validation involved in two parts, mainly retrospective validation, and internal validation. In retrospective validation redocking and retrospective docking is performed using COX 1 (pdb id 3N8Y) and COX 2(3LN0) for the validation of the forcefield molecular mechanics used in docking software. Redocking is done by RMSD value and overlay of the ligand structures obtained through docking and separated ligand structure from protein complex. Retrospective validation done through the matching of the experimental ki as well as calculated ki obtained through docking. In this study already marketed drugs taken and docked against the COX1 as well as COX2 enzyme. Scoring function in Autodock 4 was found valid as found overlaying of crystal as well as docked conformations with linear RMSD, hydrophobic interactions with active site of enzymes and linear relationship between experimental ki and Calculated ki i.e. R is equivalent to 1.

Keywords: Autodock4, scoring function, validation, force field Molecular Mechanics, COX 1, COX 2.