Extracting Atomic Contributions to Binding Free Energy Using Molecular Dynamics Simulations with Mixed Solvents (MDmix).

ABSTRACT:

Background

Mixed solvents MD (MDmix) simulations have proved to be a useful and increasingly accepted technique with several applications in structure-based drug discovery. One of the assumptions behind the methodology is the transferability of free energy values from the simulated cosolvent molecules to larger drug-like molecules. However, the binding free energy maps (ΔGbind) calculated for the different moieties of the cosolvent molecules (e.g. a hydroxyl map for the ethanol) are largely influenced by the rest of the solvent molecule and do not reflect the intrinsic affinity of the moiety in question. As such, they are hardly transferable to different molecules.

Method

To achieve transferable energies, we present here a method for decomposing the molecular binding free en

SUBMITTER: Alvarez-Garcia D 

PROVIDER: S-EPMC9906626 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature