Protein-Ligand CH-π Interactions: Structural Informatics, Energy Function Development, and Docking Implementation.
J Chem Theory Comput
; 19(16): 5503-5515, 2023 Aug 22.
Article
em En
| MEDLINE
| ID: mdl-37493980
ABSTRACT
Here, we develop an empirical energy function based on quantum mechanical data for the interaction between methane and benzene that captures the contribution from CH-π interactions. Such interactions are frequently observed in protein-ligand crystal structures, particularly for carbohydrate ligands, but have been hard to quantify due to the absence of a model for CH-π interactions in typical molecular mechanical force fields or docking scoring functions. The CH-π term was added to the AutoDock Vina (AD VINA) scoring function enabling its performance to be evaluated against a cohort of more than 1600 occurrences in 496 experimental structures of protein-ligand complexes. By employing a conformational grid search algorithm, inclusion of the CH-π term was shown to improve the prediction of the preferred orientation of flexible ligands in protein-binding sites and to enhance the detection of carbohydrate-binding sites that display CH-π interactions. Last but not least, this term was also shown to improve docking performance for the CASF-2016 benchmark set and a carbohydrate set.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Simulação de Acoplamento Molecular
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Chem Theory Comput
Ano de publicação:
2023
Tipo de documento:
Article