Identification of Novel Cyclin A2 Binding Site and Nanomolar Inhibitors of Cyclin A2-CDK2 Complex.

ABSTRACT:

Background

Given the diverse roles of cyclin A2 both in cell cycle regulation and in DNA damage response, identifying small molecule regulators of cyclin A2 activity carries significant potential to regulate diverse cellular processes in both ageing/neurodegeneration and in cancer.

Objective

Based on cyclin A2's recently discovered role in DNA repair, we hypothesized that small molecule inhibitors that were predicted to bind to both cyclin A2 and CDK2 will be useful as a radiosensitizer of cancer cells. In this study, we used structure-based drug discovery to find inhibitors that target both cyclin A2 and CDK2.

Methods

Molecular dynamics simulations were used to generate diverse binding pocket conformations for application of the relaxed complex scheme. We then used s

SUBMITTER: Kim SS 

PROVIDER: S-EPMC7326642 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature