TY - JOUR
T1 - Tuning Local Hydration Enables a Deeper Understanding of Protein-Ligand Binding
T2 - The PP1-Src Kinase Case
AU - Spitaleri, Andrea
AU - Zia, Syeda R.
AU - Di Micco, Patrizio
AU - Al-Lazikani, Bissan
AU - Soler, Miguel A.
AU - Rocchia, Walter
N1 - Publisher Copyright:
©
PY - 2021/1/14
Y1 - 2021/1/14
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jpclett.0c03075
DO - 10.1021/acs.jpclett.0c03075
M3 - Article
C2 - 33300337
AN - SCOPUS:85099018202
SN - 1948-7185
VL - 12
SP - 49
EP - 58
JO - Journal of Physical Chemistry Letters
JF - Journal of Physical Chemistry Letters
IS - 1
ER -