当前位置： SCI文献检索 > BMC BIOINFORMATICS期刊下所有文献 > Machine-learning scoring functions for identifying native poses of ligands docked to known and novel proteins.

Machine-learning scoring functions for identifying native poses of ligands docked to known and novel proteins.

Abstract：

BACKGROUND:Molecular docking is a widely-employed method in structure-based drug design. An essential component of molecular docking programs is a scoring function (SF) that can be used to identify the most stable binding pose of a ligand, when bound to a receptor protein, from among a large set of candidate poses. Despite intense efforts in developing conventional SFs, which are either force-field based, knowledge-based, or empirical, their limited docking power (or ability to successfully identify the correct pose) has been a major impediment to cost-effective drug discovery. Therefore, in this work, we explore a range of novel SFs employing different machine-learning (ML) approaches in conjunction with physicochemical and geometrical features characterizing protein-ligand complexes to predict the native or near-native pose of a ligand docked to a receptor protein's binding site. We assess the docking accuracies of these new ML SFs as well as those of conventional SFs in the context of the 2007 PDBbind benchmark dataset on both diverse and homogeneous (protein-family-specific) test sets. Further, we perform a systematic analysis of the performance of the proposed SFs in identifying native poses of ligands that are docked to novel protein targets. RESULTS AND CONCLUSION:We find that the best performing ML SF has a success rate of 80% in identifying poses that are within 1 Å root-mean-square deviation from the native poses of 65 different protein families. This is in comparison to a success rate of only 70% achieved by the best conventional SF, ASP, employed in the commercial docking software GOLD. In addition, the proposed ML SFs perform better on novel proteins that they were never trained on before. We also observed steady gains in the performance of these scoring functions as the training set size and number of features were increased by considering more protein-ligand complexes and/or more computationally-generated poses for each complex.

journal_name

BMC Bioinformatics

journal_title

BMC bioinformatics

authors

Ashtawy HM,Mahapatra NR

doi

10.1186/1471-2105-16-S6-S3

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

issn

1471-2105

pii

1471-2105-16-S6-S3

journal_volume

16 Suppl 6

pub_type

杂志文章

在线工具

Machine-learning scoring functions for identifying native poses of ligands docked to known and novel proteins.