Multiple Poses and Thermodynamics of Ligands Targeting Protein Surfaces: The Case of Furosemide Binding to mitoNEET in Aqueous Solution.

ABSTRACT: Human NEET proteins, such as NAF-1 and mitoNEET, are homodimeric, redox iron-sulfur proteins characterized by triple cysteine and one histidine-coordinated [2Fe-2S] cluster. They exist in an oxidized and reduced state. Abnormal release of the cluster is implicated in a variety of diseases, including cancer and neurodegeneration. The computer-aided and structure-based design of ligands affecting cluster release is of paramount importance from a pharmaceutical perspective. Unfortunately, experimental structural information so far is limited to only one ligand/protein complex. This is the X-ray structure of furosemide bound to oxidized mitoNEET. Here we employ an enhanced sampling approach, Localized Volume-based Metadynamics, developed by some of us, to identify binding poses of furosemide t

SUBMITTER: Hoang LG 

PROVIDER: S-EPMC9086288 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature