Tuning Local Hydration Enables a Deeper Understanding of Protein-Ligand Binding: The PP1-Src Kinase Case.
J Phys Chem Lett
; 12(1): 49-58, 2021 Jan 14.
Article
in En
| MEDLINE
| ID: mdl-33300337
ABSTRACT
Water plays a key role in biomolecular recognition and binding. Despite the development of several computational and experimental approaches, it is still challenging to comprehensively characterize water-mediated effects on the binding process. Here, we investigate how water affects the binding of Src kinase to one of its inhibitors, PP1. Src kinase is a target for treating several diseases, including cancer. We use biased molecular dynamics simulations, where the hydration of predetermined regions is tuned at will. This computational technique efficiently accelerates the SRC-PP1 binding simulation and allows us to identify several key and yet unexplored aspects of the solvent's role. This study provides a further perspective on the binding phenomenon, which may advance the current drug design approaches for the development of new kinase inhibitors.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Src-Family Kinases
/
Protein Kinase Inhibitors
Language:
En
Journal:
J Phys Chem Lett
Year:
2021
Document type:
Article
Affiliation country:
Italy