Binding Affinity Prediction by Pairwise Function Based on Neural Network
- 22 June 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Chemical Information and Modeling
- Vol. 60 (6), 2766-2772
- https://doi.org/10.1021/acs.jcim.0c00026
Abstract
We present a new approach to estimate the binding affinity from given three-dimensional poses of protein-ligand complexes. In this scheme, every protein-ligand atom pair makes an additive free-energy contribution. The sum of these pairwise contributions then gives the total binding free energy or the logarithm of the dissociation constant. The pairwise contribution is calculated by a function implemented via a neural network that takes the properties of the two atoms and their distance as input. The pairwise function is trained using a portion of the PDBbind 2018 data set. The model achieves good accuracy for affinity predictions when evaluated with PDBbind 2018 and with the CASF-2016 benchmark, comparing favorably to many scoring functions such as that of AutoDock Vina. The framework here may be extended to incorporate other factors to further improve its accuracy and power.Funding Information
- American Heart Association (TC02274)
This publication has 28 references indexed in Scilit:
- PotentialNet for Molecular Property PredictionACS Central Science, 2018
- Advancing Drug Discovery through Enhanced Free Energy CalculationsAccounts of Chemical Research, 2017
- Protein–Ligand Scoring with Convolutional Neural NetworksJournal of Chemical Information and Modeling, 2017
- Classification of Current Scoring FunctionsJournal of Chemical Information and Modeling, 2015
- Accurate and Reliable Prediction of Relative Ligand Binding Potency in Prospective Drug Discovery by Way of a Modern Free-Energy Calculation Protocol and Force FieldJournal of the American Chemical Society, 2015
- Comparative Assessment of Scoring Functions on a Diverse Test SetJournal of Chemical Information and Modeling, 2009
- Assessment of programs for ligand binding affinity predictionJournal of Computational Chemistry, 2008
- The Many Roles of Computation in Drug DiscoveryScience, 2004
- Thermodynamics of Protein–Ligand Interactions: History, Presence, and Future AspectsJournal of Receptors and Signal Transduction, 2004
- Recent developments in structure-based drug designJournal of Molecular Medicine, 2000