{Reference Type}: Journal Article
{Title}: Tuning Local Hydration Enables a Deeper Understanding of Protein-Ligand Binding: The PP1-Src Kinase Case.
{Author}: Spitaleri A;Zia SR;Di Micco P;Al-Lazikani B;Soler MA;Rocchia W;
{Journal}: J Phys Chem Lett
{Volume}: 12
{Issue}: 1
{Year}: Jan 2021 14
{Factor}: 6.888
{DOI}: 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.