Exploration of the selective binding mechanism of protein kinase Aurora A selectivity via a comprehensive molecular modeling study.

ABSTRACT:

Background

The kinase of Aurora A has been regarded as a promising therapeutic target due to its altered expression in various human cancers. However, given the high similarity of the active binding site of Aurora A to other kinases, designing highly selective inhibitors towards Aurora A remains a challenge. Recently, two potential small-molecule inhibitors named AT9283 and Danusertib were reported to exhibit significant selectivity to Aurora A, but not to Gleevec. It was argued that protein dynamics is crucial for drug selectivity to Aurora A. However, little computational research has been conducted to shed light on the underlying mechanisms.

Methods

In this study, MM/GBSA calculations based on conventional molecular dynamics (cMD) simulations and enhanced sampling simulat

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC6814069 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature