Inherited Eye Disease-Related Proteins: Molecular Modeling and Global Computational Mutagenesis

Inherited eye diseases are caused by genetic mutations affecting protein structure and function. The genetic perturbations cause a change in protein activity or even a complete loss of the affected protein in the metabolic pathway and at the cellular level. This could influence a change in the inherited disease phenotype. At the present, understanding of the roles of genetic mutations in human disease is harmed by the absence of a link between structural perturbations at the atomic level of protein and the clinical significance of the mutation. The changes in protein associated with missense mutations might cause protein misfolding and affect protein–protein interaction sites, change the solubility, or stability of protein molecules. The structural effect of mutational changes can be analyzed computationally with the use of atomic protein structure or homology models, molecular modeling, global computational mutagenesis, and computer simulations. The parameters derived from atomic protein structure could be potentially helpful in clinical studies for in silico forecasts of the severity of structural alterations in protein caused by genetic mutation and suggests the way for the evaluation of possible changes in the disease phenotype.