Work

Implicit ligand theory for relative binding free energies

Year: 2018

Type: article

Abstract: Implicit ligand theory enables noncovalent binding free energies to be calculated based on an exponential average of the binding potential of mean force (BPMF)-the binding free energy between a flexible ligand and rigid receptor-over a precomputed ensemble of receptor configurations. In the original formalism, receptor configurations were drawn from or reweighted to the apo ensemble. Here we show that BPMFs averaged over a holo ensemble yield binding free energies relative to the reference ligand that specifies the ensemble. When using receptor snapshots from an alchemical simulation with a single ligand, the new statistical estimator outperforms the original.

Source: The Journal of Chemical Physics

DOI: 10.1063/1.5017136

Authors: Trung Hai Nguyen, David D. L. Minh

Institution: Illinois Institute of Technology

Language: English

Topic: Computational Drug Discovery Methods

Subfield: Computational Theory and Mathematics

Field: Computer Science

Domain: Physical Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences

Award: Sound-stage Virtual Screening Based on Implicit Ligand Theory