In silico analysis of D107Y, R130Y, and R335H mutations in PTEN protein and their relationship with prostate cancer

Prostate cancer (PCa) is the second most commonly diagnosed cancer worldwide and the most frequent cancer among men in Mexico, with Sinaloa reporting the highest incidence (GLOBOCAN 2022). PCa arises from uncontrolled proliferation of malignant prostate cells, with multiple contributing factors including genetic alterations such as mutations in the tumor suppressor gene PTEN, a key regulator of the PI3K/AKT pathway. Through a systematic literature review and bioinformatics analysis (NCBI, PDB, UniProt, UCSF Chimera, WinCoot, Mutation3D, SNPs&GO, I-Mutant 2.0, PyMOL 3.0), 30 PTEN mutations associated with PCa were identified. Among these, D107Y, R130Y, and R335H were selected for in silico structural and functional analysis due to their predicted deleterious effects and significant structural changes. Structural modeling confirmed high-quality PTEN models, while Mutation3D and PyMOL analyses revealed that R130Y and R335H induce alterations in bond formation and tertiary structure, potentially affecting phosphatase activity and membrane anchoring. SNP-based predictions suggest that all three mutations may impair PTEN function, although experimental validation is required. These findings highlight the potential impact of specific PTEN mutations on protein stability and function in PCa and propose these variants as targets for future in vitro studies to explore their utility as molecular markers for diagnosis.