Development of Postprocessing Method of Protein-Ligand Docking using Interaction Fingerprint

Abstract

Protein-ligand docking is an important method in Structure-based Drug Discovery [1]. Although many programs have been developed for docking [2], the accuracy is still insufficient due to the difficulty in the scoring function [3]. Interaction fingerprint is one of the solutions, which generate fingerprints of ligands using the interactions between the ligand and the protein. Interaction fingerprints use the information of known compounds so that compounds that have similar interaction to the known active ligands are expected to find through the virtual screening. However, existing interaction fingerprints such as SIFt [4] and SPLIF [5] only assess the existence or the distance of the interactions and do not consider the strength correctly. In this study, we made a new scoring function of protein-ligand docking called SIEVE-Score (Similarity of Interaction Energy VEctor-Score), which can consider the strength of each interaction explicitly. SIEVE-Score is calculated based on the similarity of the interaction energy vector, which is the list of interaction energy between the ligand and each residue of the protein. We also evaluate the accuracy of virtual screening using SIEVE-Score after the docking by Glide [6].[1] Chiba, S., et al. Identification of potential inhibitors based on compound proposal contest: Tyrosine-protein kinase Yes as a target. Scientific reports 5:17209, 2015.[2] Elizabeth Y., Jessica H., and Paul A. R., Improvements, trends, and new ideas in molecular docking: 2012–2013 in review. Journal of Molecular Recognition, 28(10):581–604, 2015.[3] Yan L., Li H., Zhihai L., and Renxiao W., Comparative assessment of scoring functions on an updated benchmark: 2. evaluation methods and general results. Journal of Chemical Information and Modeling, 54(6):1717–1736, 2014.[4] Zhan D., Claudio C., and Juswinder S., Structural interaction fingerprint (SIFt): a novel method for analyzing three-dimensional protein-ligand binding interactions. Journal of Medicinal Chemistry, 47(2):337–344, 2004.[5] Da C., and Kireev D., Structural protein–ligand interaction fingerprints (SPLIF) for structure- based virtual screening: Method and benchmark study. Journal of Chemical Information and Modeling, 54(9):2555–2561, 2014.[6] Richard A. F., et al., Glide: a new approach for rapid, accurate docking and scoring. 1. method and assessment of docking accuracy. Journal of Medicinal Chemistry, 47(7):1739–1749, 2004.