INSILICO INVESTIGATION OF MISSENSE MUTATIONS IN SDH5 GENE USING DIFFERENT GENOMIC ALGORITHMS
Abstract
Objective: Nonsynonymous single nucleotide polymorphism (nsSNP) has a deleterious effect on a protein, thereby leading to a disease. Succinate dehydrogenase complex 5 (SDH5) gene, which encodes for a mitochondrial protein is responsible for the flavination of succinate dehydrogenase complex and also plays a major role in Kreb's cycle. Mutations in this gene lead to the cancerous diseases such as paraganglioma and pheochromocytoma. The aim of this paper is to excavate the deleterious mutations in SDH5.
Method: The deleterious mutations in SDH5is evaluated by assorted genomic algorithmsand to find the drug binding affinity by docking the current drug against the mutated protein using Molecular docking Server. A total of 20 mutation were retrieved from SNP NCBI. The structural and the functional aspectsof these 20 mutations were analysed by using various genomics algorithmssuch as SIFT, PolyPhen2.0, I-Mutant 2.0, SNPs & GO, PANTHER and PhD-SNP, which helped us narrowing down our search to G78R and L80S as the deleterious missense mutations. The drug cyclophosphamide, used for the treatment of these cancerous diseases was considered for our study. Drug-protein interactions were studied using protein docking server. Binding efficiency of the cyclophosphamide drug with the most deleterious mutations was calculated.
Result: G78Rwas found to be deleterious and confirmed that the mutation decrease the stability of the protein.
Conclusion: Our findings lead to the better understanding of the deleterious mutations in SDH5, providing immense knowledge on the cancerous diseases, such as paraganglioma and pheochromocytoma, and drug docking mechanisms which will be extremely useful in the discovery of new treatmentsagainst such diseases.
Keywords: Cyclophosphamide, Molecular docking, Paraganglioma, Pheochromocytoma, SDH5 geneDownloads
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