Computational and drug target analysis of functional single nucleotide polymorphisms associated with Haemoglobin Subunit Beta (HBB) gene

• Published in: Computers in biology and medicine Vol. 125; p. 104018
• Main Authors: Soremekun, Opeyemi S., Ezenwa, Chisom, Isewon, Itunuoluwa, Soliman, Mahmoud, Idowu, Omotuyi, Nashiru, Oyekanmi, Fatumo, Segun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.10.2020; Elsevier Limited
• Subjects: Algorithms; Alpha thalassaemia; Amino acids; Bayesian analysis; Beta thalassaemia; Blood diseases; Chemical compounds; Computer applications; Disease; Genes; Haemoglobin subunit beta (HBB); Haemoglobinopathies; HBB gene; Hemoglobin; Informatics; Internal Medicine; Mutation; Neural networks; Nucleotides; Other; Pathogenesis; Perturbation; Pharmacology; Polymorphism; Proteins; Single nucleotide polymorphism (SNPs); Single-nucleotide polymorphism; SNP informatics; Statistical analysis; Structural stability; Support vector machines; Thalassemia; Therapeutic targets; Single nucleotide polymorphism (SNPs); Beta thalassaemia; SNP informatics; Haemoglobinopathies; Mutation; Alpha thalassaemia; Haemoglobin subunit beta (HBB)
• ISSN: 0010-4825; 1879-0534; 1879-0534
• DOI: 10.1016/j.compbiomed.2020.104018

There is overwhelming evidence implicating Haemoglobin Subunit Beta (HBB) protein in the onset of beta thalassaemia. In this study for the first time, we used a combined SNP informatics and computer algorithms such as Neural network, Bayesian network, and Support Vector Machine to identify deleterious non-synonymous Single Nucleotide Polymorphisms (nsSNPs) present in the HBB gene. Our findings highlight three major mutation points (R31G, W38S, and Q128P) within the HBB gene sequence that have significant statistical and computational associations with the onset of beta thalassaemia. The dynamic simulation study revealed that R31G, W38S, and Q128P elicited high structural perturbation and instability, however, the wild type protein was considerably stable. Ten compounds with therapeutic potential against HBB were also predicted by structure-based virtual screening. Interestingly, the instability caused by the mutations was reversed upon binding to a ligand. This study has been able to predict potential deleterious mutants that can be further explored in the understanding of the pathological basis of beta thalassaemia and the design of tailored inhibitors. •For the first time, we identify deleterious non-synonymous Single Nucleotide Polymorphisms (nsSNPs) present in the HBB gene.•Our findings highlight three major mutation points (R31G, W38S, and Q128P) within the HBB gene sequence that have significant statistical and computational associations with the onset of beta thalassaemia.•The dynamic simulation study revealed that R31G, W38S, and Q128P elicited high structural perturbation and instability, however, the wild type protein was considerably stable.