Computational Insights into the Structural and Functional Impacts of nsSNPs of Bone Morphogenetic Proteins

Abstract

BMPs (bone morphogenetic proteins) are multipurpose (transforming growth factor)TGF-superfamily released cytokines. These glycoproteins, acting as disulfide-linked homo- or heterodimers, are highly potent regulators of bone and cartilage production and repair, cell proliferation throughout embryonic development, and bone homeostasis in the adults. Due to the fact that genetic variation might influence structural functions, this study is aimed to determine the pathogenic effect of nonsynonymous single-nucleotide polymorphisms (nsSNPs) in BMP genes. The implications of these variations, investigated using computational analysis and molecular models of the mature TGF-β domain, revealed the impact of modifications on the function of BMP protein. The three-dimensional (3D) structure analysis was performed on the nsSNP Y316S, V386G, E387G, C389G, and C391G nsSNP in the TGF-β domain of chicken BMP2 and H344P, S347P, V357A nsSNP in the TGF-β domain of chicken BMP4 protein that was anticipated to be harmful and of high risk. The ability of the proteins to perform variety of tasks interact with other molecules depends on their tertiary structural composition. The current analysis revealed the four most damaging variants (Y316S, V386G, E387G, C389G, and C391G), highly conserved and functional and are located in the TGF-beta domain of BMP2 and BMP4. The amino acid substitutions E387G, C389G, and C391G are discovered in the binding region. It was observed that the mutations in the TGF-beta domain caused significant changes in its structural organization including the substrate binding sites. Current findings will assist future research focused on the role of these variants in BMP function loss and their role in skeletal disorders, and this will possibly help to develop practical strategies for treating bone-related conditions.

[Retracted] In Silico Structural and Functional Analyses of NLRP3 Inflammasomes to Provide Insights for Treating Neurodegenerative Diseases

“…We searched for the human NLRP3 nucleotide and amino acid sequences in the online databases of Ensembl (ENSG00000162711) [ 18 ] and the National Centre for Biotechnology Information (NCBI) ( https://www.ncbi.nlm.nih.gov ) [ 19 ]. Ensembl is a part of the National Institutes of Health.…”

“…Additionally, utilising the LPIcom web server, residues, preferred interactions, and binding motifs for a specific ligand were predicted. All target proteins' domains were looked up in NLRP3 using InterProScan [ 35 ] and the protein domain database [ 19 ]. The photos were then precisely and succinctly visualised using DOG 2 software [ 36 ].…”

Genome-wide identification and structural analysis of the BMP gene family in Triplophysa dalaica

“…The BMP gene family comprises essential signaling molecules involved in regulating cell division, proliferation, function, and tissue morphogenesis [ 39 ]. Furthermore, due to their significance as growth factors, they have a wide range of potential applications in various industries, including skeletal disease therapy and regenerative medicine [ 40 , 41 ].…”

A Simulation Analysis and Screening of Deleterious Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) in Sheep LEP Gene

“…Highly conserved functional regions of the protein coded by the LEP gene was identified by ConSurf tool (http://consurf.tau.ac.il/) [25][26][27].…”