Integrating State-of-the-Art in silico Tools With Molecular Docking to Predict the Impact of the Most Deleterious Amino Acid Substitutions on TRAPPC6A Protein

Trafficking Protein Particle Complex subunit 6A (TRAPPC6A) is an important molecule that is mainly involved in the transport of vesicles to the cis-Golgi membrane. Loss of function in this protein leads to a variety of severe disorders. The present study was conducted to prioritize the most deleterious effects of non-synonymous single nucleotide polymorphisms (nsSNPs) on TRAPPC6A protein. Two approaches were employed, sequence-based and structure-based, to predict which nsSNP has the most harmful effects on TRAPPC6A. Docking was performed to compare the ability of normal TRAPPC6A and its most delete-rious mutants to bind with the corresponding recep-tor. All utilized in silico tools indicated highly damaging impacts of three nsSNPs, viz. W74C, G125S and G129D. Docking showed remarkable alterations in the atomic contact energy of TRAPPC6A binding with its receptor. The present finding provides a cost effective method for assessing the damaging effects of nsSNPs on TRAPPC6A, which may help in under-standing the impact of this protein on neurodevelop-mental disorders.