P38α MAPK and Type I inhibitors: Binding site analysis and use of target ensembles in virtual screening

17Citations
Citations of this article
28Readers
Mendeley users who have this article in their library.

Abstract

Mitogen-activated protein kinase p38α plays an essential role in the regulation of pro-inflammatory signaling, and selective blockade of this kinase could be efficacious in many pathological processes. Despite considerable research efforts focused on the discovery and development of p38α MAPK inhibitors, no drug targeting this protein has been approved for clinical use so far. We herein analyze the available crystal structures of p38α MAPK in complex with ATP competitive type I inhibitors, getting insights into ATP binding site conformation and its influence on automated molecular docking results. The use of target ensembles, rather than single conformations, resulted in a performance improvement in both the ability to reproduce experimental bound conformations and the capability of mining active molecules from compound libraries. The information gathered from this study can be exploited in structure-based drug discovery programs having as the ultimate aim the identification of novel p38α MAPK type I inhibitors.

Cite

CITATION STYLE

APA

Astolfi, A., Iraci, N., Sabatini, S., Barreca, M. L., & Cecchetti, V. (2015). P38α MAPK and Type I inhibitors: Binding site analysis and use of target ensembles in virtual screening. Molecules, 20(9), 15842–15861. https://doi.org/10.3390/molecules200915842

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free