VAD-MM/GBSA: A Variable Atomic Dielectric MM/GBSA Model for Improved Accuracy in Protein-Ligand Binding Free Energy Calculations.
J Chem Inf Model
; 61(6): 2844-2856, 2021 06 28.
Article
em En
| MEDLINE
| ID: mdl-34014672
ABSTRACT
The molecular mechanics/generalized Born surface area (MM/GBSA) has been widely used in end-point binding free energy prediction in structure-based drug design (SBDD). However, in practice, it is usually being treated as a disputed method mostly because of its system dependence. Here, combining with machine-learning optimization, we developed a novel version of MM/GBSA, named variable atomic dielectric MM/GBSA (VAD-MM/GBSA), by assigning variable dielectric constants directly to the protein/ligand atoms. The new strategy exhibits markedly improved accuracy in binding affinity calculations for various protein-ligand systems and is promising to be used in the postprocessing of structure-based virtual screening. Moreover, VAD-MM/GBSA outperformed prime MM/GBSA in Schrödinger software and showed remarkable predictive performance for specific protein targets, such as POL polyprotein, human immunodeficiency virus type 1 (HIV-1) protease, etc. Our study showed that the VAD-MM/GBSA method with little extra computational overhead provides a potential replacement of the MM/GBSA in AMBER software. An online web server of VAD-MMGBSA has been developed and is now available at http//cadd.zju.edu.cn/vdgb.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Simulação de Dinâmica Molecular
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article