Biomedical Letters

Homology modeling, molecular docking and virtual screening to reveal potential inhibitor of ALS associated protein guanine nucleotide exchange C9ORF72

Syeda Maheen Abid 1*, Muhammad Ali 2

1 Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad, Pakistan

2 District Head Quarter Hospital, Chiniot, Pakistan

Abstract

Repeated expansion of hexanucleotide in C9ORF72 encodes the protein Guanine Nucleotide Exchange considered as the main cause of Amyotrophic Lateral Sclerosis (ALS). The repeated expansion produces toxic products and autophagy deficits. Various in silico approaches were employed for structural 3D modeling and protein-protein molecular docking analyses of C9ORF72 followed by virtual screening. Homology modeling and threading approaches were applied to predict the 3D structures of C9ORF72 and 92.38% of quality factor was calculated by ERRAT evaluation tool. STRING database was utilized, and it was observed that SMCR8 has the ability to be the interacting partner of C9ORF72. Protein-protein molecular docking analyses of C9ORF72 with SMCR8 were performed and potential interacting residues were observed computationally. FDA library from ZINC database was utilized for virtual screening and comparative molecular docking analyses were performed by AutoDock Vina. It was proposed that the scrutinized compound ZINC131 have strong binding affinities and least binding energy of -11.3 kcal/mol. The suggested molecule may be used for further analyses in the drug discovery processes. The predicted 3D structure of C9ORF72 provides the structural insights for the better functional understanding of C9ORF72. Overall, the findings of present work may be helpful in designing the novel therapeutic targets against C9ORF72.