Tuning Local Hydration Enables a Deeper Understanding of Protein-Ligand Binding: The PP1-Src Kinase Case
Articolo
Data di Pubblicazione:
2021
Citazione:
Tuning Local Hydration Enables a Deeper Understanding of Protein-Ligand Binding: The PP1-Src Kinase Case / A. Spitaleri, S.R. Zia, P. Di Micco, B. Al-Lazikani, M.A. Soler, W. Rocchia. - In: THE JOURNAL OF PHYSICAL CHEMISTRY LETTERS. - ISSN 1948-7185. - 12:1(2021), pp. 49-58. [10.1021/acs.jpclett.0c03075]
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.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
A. Spitaleri, S.R. Zia, P. Di Micco, B. Al-Lazikani, M.A. Soler, W. Rocchia
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