Comparative Analyses of the Relative Effects of Various Mutations in Major Histocompatibility Complex I-a Way to Predict Protein-Protein Interactions

摘要

Protein-protein interactions (PPIs) play pivotal roles in most of the biological processes. PPI dysfunctions are therefore associated with disease situations. Mutations often lead to PPI dysfunctions, but there are certain other types of mutations which do not cause any appreciable abnormalities. This second type of mutations is called polymorphic mutations. So far, there are many studies that deal with the identification of PPI sites, but clear-cut analyses of the involvements of mutations in PPI dysfunctions are few and far between. We therefore made an attempt to link the appearances of mutations and PPI disruptions. We used major histocompatibility complex as our reference protein complex. We analyzed the mutations leading to the disease amyloidosis and also the other mutations that do not lead to disease conditions. We computed various biophysical parameters like relative solvent accessibility to discriminate between the two different types of mutations. Our analyses for the first time came up with a plausible explanation for the effects of different types of mutations in disease development. Our future plans are to build tools to detect the effects of mutations in disease developments by disrupting the PPIs.