Work

Secondary Binding Site of CYP17A1 in Enhanced Sampling Simulations

Year: 2024

Type: article

Abstract: Androgens like testosterone and dihydrotestosterone play a key role in prostate cancer progression, making the enzyme CYP17A1, essential for androgen synthesis, a crucial therapeutic target. Recent studies have revealed electron density at the substrate entry channel, suggesting the presence of a secondary binding site. In this study, we calculated the binding free energy landscape of known ligands at this site using Funnel Metadynamics. Our results characterize this binding site and indicate that nonheme-interacting ligands could effectively bind to CYP17A1, providing a novel approach to the design of CYP17A1 inhibitors.

Source: Journal of Chemical Information and Modeling

DOI: 10.1021/acs.jcim.4c01293

Authors: Tomasz M. Wróbel, Damian Bartuzi, Agnieszka A. Kaczor

Institutions: Medical University of Lublin, University of Copenhagen, Uppsala University, Science for Life Laboratory, University of Eastern Finland

Language: English

Topic: Computational Drug Discovery Methods

Subfield: Computational Theory and Mathematics

Field: Computer Science

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funders: Partnership for Advanced Computing in Europe AISBL, Narodowe Centrum Nauki, Narodowa Agencja Wymiany Akademickiej