A missense mutation is a point mutation of a gene that determines a single amino acid change in the gene product (the encoded protein). Missense mutations may have a deleterious impact in the folding and conformation stability of the affected protein. As a consequence, proteins affected by missense mutations may present an aberrant function, expression or localization, and be involved in the development of inherited diseases.
Part of our team is dedictated to the development of novel in silico strategies aimed at predicting the potential pathogenic effect of missense mutations in proteins with key roles in cellular and phisiological processes, with the aim of providing clinicians with a great help to decipher the cause of genetic diseases in patients diagnosed with missense mutations.
Currently, our studies are focused on pathogenicity predictions of missense mutations involving human RPE65, a fundamental enzyme of the retinoid visual cycle involved in pathological phenotypes such as retinitis pigmentosa and leber congenital amaurosis.
An in silico toolbox for the prediction of the potential pathogenic effects of missense mutations in the dimeric region of hRPE65. Poli G, Demontis GC, Sodi A, Saba A, Rizzo S, Macchia M, Tuccinardi T. J Enzyme Inhib Med Chem. 2023, 38(1):2162047.
Predicting potentially pathogenic effects of hRPE65 missense mutations: a computational strategy based on molecular dynamics simulations. Poli G, Barravecchia I, Demontis GC, Sodi A, Saba A, Rizzo S, Macchia M, Tuccinardi T. J Enzyme Inhib Med Chem. 2022, 37(1):1765-1772.