Predicting binding events in very flexible, allosteric, multi-domain proteins.

ABSTRACT: Knowledge of the structures formed by proteins and small molecules is key to understand the molecular principles of chemotherapy and for designing new and more effective drugs. During the early stage of a drug discovery program, it is customary to predict ligand-protein complexes in silico, particularly when screening large compound databases. While virtual screening based on molecular docking is widely used for this purpose, it generally fails in mimicking binding events associated with large conformational changes in the protein, particularly when the latter involve multiple domains. In this work, we describe a new methodology to generate bound-like conformations of very flexible and allosteric proteins bearing multiple binding sites by exploiting only information on the unbound s

SUBMITTER: Basciu A 

PROVIDER: S-EPMC11185556 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature