Incorporating Explicit Water Molecules and Ligand Conformation Stability in Machine-Learning Scoring Functions

J Chem Inf Model. 2019 Nov 25;59(11):4540-4549. doi: 10.1021/acs.jcim.9b00645. Epub 2019 Oct 31.

Abstract

Structure-based drug design is critically dependent on accuracy of molecular docking scoring functions, and there is of significant interest to advance scoring functions with machine learning approaches. In this work, by judiciously expanding the training set, exploring new features related to explicit mediating water molecules as well as ligand conformation stability, and applying extreme gradient boosting (XGBoost) with Δ-Vina parametrization, we have improved robustness and applicability of machine-learning scoring functions. The new scoring function ΔvinaXGB can not only perform consistently among the top compared to classical scoring functions for the CASF-2016 benchmark but also achieves significantly better prediction accuracy in different types of structures that mimic real docking applications.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Databases, Protein
  • Drug Design*
  • Humans
  • Ligands
  • Machine Learning*
  • Molecular Conformation
  • Molecular Docking Simulation
  • Protein Binding
  • Proteins / chemistry
  • Proteins / metabolism*
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology*
  • Water / chemistry*
  • Water / metabolism

Substances

  • Ligands
  • Proteins
  • Small Molecule Libraries
  • Water