Ligand Binding Path Sampling Based on Parallel Cascade Selection Molecular Dynamics: LB-PaCS-MD.
Materials (Basel)
; 15(4)2022 Feb 17.
Article
em En
| MEDLINE
| ID: mdl-35208030
ABSTRACT
Parallel cascade selection molecular dynamics (PaCS-MD) is a rare-event sampling method that generates transition pathways between a reactant and product. To sample the transition pathways, PaCS-MD repeats short-time MD simulations from important configurations as conformational resampling cycles. In this study, PaCS-MD was extended to sample ligand binding pathways toward a target protein, which is referred to as LB-PaCS-MD. In a ligand-concentrated environment, where multiple ligand copies are randomly arranged around the target protein, LB-PaCS-MD allows for the frequent sampling of ligand binding pathways. To select the important configurations, we specified the center of mass (COM) distance between each ligand and the relevant binding site of the target protein, where snapshots generated by the short-time MD simulations were ranked by their COM distance values. From each cycle, snapshots with smaller COM distance values were selected as the important configurations to be resampled using the short-time MD simulations. By repeating conformational resampling cycles, the COM distance values gradually decreased and converged to constants, meaning that a set of ligand binding pathways toward the target protein was sampled by LB-PaCS-MD. To demonstrate relative efficiency, LB-PaCS-MD was applied to several proteins, and their ligand binding pathways were sampled more frequently than conventional MD simulations.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Materials (Basel)
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Japão