| Abstrakt: |
The chromodomain helicase DNA-binding protein 7 (CHD7) is also known as ATP-dependent helicase CHD7. In humans, the CHD7 geneencodes it.Heterozygous mutations in this protein cause aggregation and have been linked to the development of the CHARGE syndrome. CHD7 is known to be a subcategory of CHD proteins identified only in metazoans containing the BRK domain. Numerous studies suggest that the protein’s functional activity is affected by non-synonymous single nucleotide polymorphisms (nsSNPs). Using computational methods, this study predicted and analyzed the most deleterious nsSNPs for their functional effect on the CHD7 protein. Eight computational tools: PhD-SNP, Polyphen-1, Polyphen-2, SIFT, SNAP, I-Mutant, MUpro, and iStable were used to predict the deleterious and unstable nsSNPs. Based on the structure availability (2V0F with the mutational position 2631–2715) and the study reported by Bartels et al., two highly deleterious nsSNPs (P2683S and R2702C) were selected, which were predicted to be deleterious and unstable from pathogenicity analysis and stability analysis. The nsSNPs (P2683S and R2702C) were determined to fall under the conserved region of the protein using the ConSurf server. The Swiss PDB viewer and PyMOL software version 2.0 were used to conduct the structural analysis of the proteins. GROMACS was used for molecular dynamics simulation to understand the stability of wild and mutant structures. In silico study indicated that P2683S will be more deleterious among the two widely studied nsSNPs. In this current study, docking analysis was performed to determine drug activity against hypogonadotropic hypogonadism associated with CHARGE syndrome. Finally, molecular docking was performed for the wild and the mutant structure P2683S to study the binding efficacy of the existing drugs Methyltestosterone and Estradiol, resulting in a similar score with a minimal difference between each other. Detailed studies about the disease, the effect of nsSNPs, and the response of the drug towards the mutation are the critical factors to launch a new personalized medicine. Experimental biologists will use the findings of our investigation to understand the variations in the CDH7 protein better. |
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