Bootstrap-based consensus scoring method for protein-ligand docking

Journal of Chemical Information and Modeling
Hiroaki FukunishiJiro Shimada

Abstract

To improve the performance of a single scoring function used in a protein-ligand docking program, we developed a bootstrap-based consensus scoring (BBCS) method, which is based on ensemble learning. BBCS combines multiple scorings, each of which has the same function form but different energy-parameter sets. These multiple energy-parameter sets are generated in two steps: (1) generation of training sets by a bootstrap method and (2) optimization of energy-parameter set by a Z-score approach, which is based on energy landscape theory as used in protein folding, against each training set. In this study, we applied BBCS to the FlexX scoring function. Using given 50 complexes, we generated 100 training sets and obtained 100 optimized energy-parameter sets. These parameter sets were tested against 48 complexes different from the training sets. BBCS was shown to be an improvement over single scoring when using a parameter set optimized by the same Z-score approach. Comparing BBCS with the original FlexX scoring function, we found that (1) the success rate of recognizing the crystal structure at the top relative to decoys increased from 33.3% to 52.1% and that (2) the rank of the crystal structure improved for 54.2% of the complexes a...Continue Reading

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Citations

May 28, 2009·Journal of Computer-aided Molecular Design·Markus H J Seifert
Nov 10, 2011·Journal of Chemical Information and Modeling·Sorin AvramLudovic Kurunczi
Jan 11, 2012·Journal of Computer-aided Molecular Design·Oliver KorbThomas E Exner
Jan 2, 2014·Pharmacological Reviews·Gregory SliwoskiEdward W Lowe
Sep 3, 2010·Journal of Computational Chemistry·Dariusz PlewczynskiKrzysztof Ginalski

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