Computing Relative Binding Affinity of Ligands to Receptor: An Effective Hybrid Single-Dual-Topology Free-Energy Perturbation Approach in NAMD.

ABSTRACT: An effective hybrid single-dual-topology protocol is designed for the calculation of relative binding affinities of small ligands to a receptor. The protocol was developed as an extension of the NAMD molecular dynamics program, which exclusively supports a dual-topology framework for relative alchemical free-energy perturbation (FEP) calculations. In this protocol, the alchemical end states are represented as two separate molecules sharing a common substructure identified through maximum structural mapping. Within the substructure, an atom-to-atom correspondence is established, and each pair of corresponding atoms is holonomically constrained to share identical coordinates at all time throughout the simulation. The forces are projected and combined at each step for propagation. Following t

SUBMITTER: Jiang W 

PROVIDER: S-EPMC7007809 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature