Protein-Protein Docking and Structural Prediction of KMT2C Variant from Cervical Cancer Whole Exome Sequencing Data

Abstract

Cervical cancer is one of the most frequent cancers among women and the fourth leading cancer for mortality worldwide, and it is caused by persistent infections of Human papillomavirus (HPV). Most of the death cases are reported in developing countries like Africa and Southeast Asia. As the incidence and mortality rates increase globally, women with advanced and recurrent cancers are showing less response towards chemoradiotherapy. Hence, molecular therapies and targets show promising results. In our study, we have performed whole exome sequencing of 10 samples in a cohort and after analyzing received top mutated genes/ variants and one of the top variants in this study we focused on KMT2C rs ID 138908625 exon 8 regions Chr 7:152265083 variation C>A, T, protein structure prediction, c score, and TM value evaluated for wild type, Query 1 and Query for top 5 models of KMT2C by I TASSER. The predicted values of the models of KMT2C Query 2 show structural similarity and functional analog when compared to Query 1 with wild-type KMT2C. Further, protein-protein docking studies were performed using Cluspro 2.0 with the compounds of Arteminisin, Shikonin, Sitoinoside IX, Bucidarasin A, and Betulin with KMT2C. The Betulin shows better binding energy (-12.5 Kcal/mol) and followed by Bucidarasin (-12.3Kcal/mol) with KMT2C. The present study is the combination of insilico work with the whole exome sequencing variants, that can be used in the prognosis and diagnosis of cervical cancer. The docking studies predict the molecular binding affinities of the ligand and the protein fold conformations.