Beyond Docking: A Multitier Computational Pipeline for USP7 Inhibitor Optimization.

ABSTRACT: Ubiquitin-specific protease 7 (USP7) is a key deubiquitinating enzyme involved in tumor suppression, DNA repair, and epigenetic regulation. Given its critical role in cancer progression, USP7 has emerged as an attractive therapeutic target. Using similarity-based ligand screening, structurally related analogs of previously identified and validated hit compounds by our research group are selected and grid-based docking simulations are performed, prioritizing molecules with high binding affinity (docking scores < -8.0 kcal mol^-1). The top-ranked candidates are refined through long molecular dynamics (MD) simulations and MM/GBSA free energy calculations to assess their structural stability and interaction patterns with key USP7 residues. Binary QSAR analysis was further used to eva

SUBMITTER: Sayyah E 

PROVIDER: S-EPMC12368476 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature