BgN-Score and BsN-Score: bagging and boosting based ensemble neural networks scoring functions for accurate binding affinity prediction of protein-ligand complexes

BMC Bioinformatics
Hossam M Ashtawy, Nihar R Mahapatra

Abstract

Accurately predicting the binding affinities of large sets of protein-ligand complexes is a key challenge in computational biomolecular science, with applications in drug discovery, chemical biology, and structural biology. Since a scoring function (SF) is used to score, rank, and identify drug leads, the fidelity with which it predicts the affinity of a ligand candidate for a protein's binding site has a significant bearing on the accuracy of virtual screening. Despite intense efforts in developing conventional SFs, which are either force-field based, knowledge-based, or empirical, their limited predictive power has been a major roadblock toward cost-effective drug discovery. Therefore, in this work, we present novel SFs employing a large ensemble of neural networks (NN) in conjunction with a diverse set of physicochemical and geometrical features characterizing protein-ligand complexes to predict binding affinity. We assess the scoring accuracies of two new ensemble NN SFs based on bagging (BgN-Score) and boosting (BsN-Score), as well as those of conventional SFs in the context of the 2007 PDBbind benchmark that encompasses a diverse set of high-quality protein families. We find that BgN-Score and BsN-Score have more than 25%...Continue Reading

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Citations

Mar 10, 2012·PloS One·Cristian Obiol-PardoJaime Rubio-Martinez
Mar 3, 2018·Journal of Bioinformatics and Computational Biology·Hossam M Ashtawy, Nihar R Mahapatra
Jun 5, 2020·Briefings in Bioinformatics·Guo-Li XiongDong-Sheng Cao
Oct 16, 2018·Frontiers in Pharmacology·Isabella A GuedesLaurent E Dardenne
Nov 20, 2016·Journal of Computational Chemistry·Cheng Wang, Yingkai Zhang
Mar 17, 2019·Interdisciplinary Sciences, Computational Life Sciences·Jin LiLe Zhang
Jul 17, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yusuf O AdeshinaJohn Karanicolas
Apr 4, 2021·International Journal of Molecular Sciences·Zihao ChenGe Zhang
May 12, 2020·Journal of Chemical Information and Modeling·Hussein Hassan-HarrirouThomas Lemmin
Jun 11, 2021·Journal of Cheminformatics·Andrew T McNuttDavid Ryan Koes
Jul 12, 2019·Chemical Reviews·Xin YangShengyong Yang
Oct 15, 2020·Journal of Chemical Information and Modeling·Jingxiao BaoJohn Z H Zhang
Dec 1, 2017·Journal of Chemical Information and Modeling·Hossam M Ashtawy, Nihar R Mahapatra
Dec 1, 2017·Journal of Chemical Information and Modeling·Hossam M Ashtawy, Nihar R Mahapatra
Sep 18, 2021·Chemical Biology & Drug Design·Mohammed BuleMohammad Abdollahi

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Methods Mentioned

BETA
BRT
PCA

Software Mentioned

SYBYL
nnet
Discovery Studio
ChemScore
PDBbind
Discovery
SLIDE
AffiScore
LigScore
GOLD

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