Finding Pathogenic nsSNP's and their structural effect on COPS2 using Molecular Dynamic Approach

COP9 Signalosome Subunit 2 is a highly conserved multiprotein complex which is involved in the cellular process and developmental process. It is one of the essential components in the COP9 Signalosome Complex (CSN). It is also involved in neuronal differentiation interacting with NIF3L1. The gene involved in neuronal differentiation is negatively regulated due to the transcription co-repressor interaction of NIF3L1 with COPS2. In the present study, we have evaluated the outcome for 90 non-synonymous single nucleotide polymorphisms (nsSNPs) in COPS2 gene through computational tools. After the analysis, 4 SNPs (S120C, N144S, Y159H, R173C) were found to be deleterious. The native and mutated structures were prepared using discovery studio and docked to check the interactions with NIF3L1.On the basis of ZDOCK score the top 3 mutations (N144S, Y159H, R173C) were screened out. Further to analyze the effect of amino acid substitution on the molecular structure of protein Molecular Dynamics simulation was carried out. Analysis based on RMSD, RMSF, RG, H-bond showed a significant deviation in the graph, which demonstrated conformation change and instability compared to the wild structure. As it is known mutations in COPS2 gene can disrupt the normal activity of the CSN2 protein which may cause neuronal differentiation. Our results showed N144S, Y159H and R173C mutations are to be more pathogenic and may cause disease