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

Soremekun, Opeyemi S. and Ezenwa, Chisom and Isewon, Itunuoluwa and Idowu, Omotuyi and Nashiru, Oyekanmi and Fatumo, S. (2020) Computational and drug target analysis of functional single nucleotide polymorphisms associated with Haemoglobin Subunit Beta (HBB) gene. Computers in Biology and Medicine.

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	SNP informatics Single nucleotide polymorphism (SNPs) Haemoglobin subunit beta (HBB) Beta thalassaemia Mutation Alpha thalassaemia Haemoglobinopathies
Subjects:	Q Science > QA Mathematics > QA75 Electronic computers. Computer science
Divisions:	Faculty of Engineering, Science and Mathematics > School of Electronics and Computer Science
Depositing User:	Mrs Patricia Nwokealisi
Date Deposited:	06 Aug 2021 14:16
Last Modified:	06 Aug 2021 14:16
URI:	http://eprints.covenantuniversity.edu.ng/id/eprint/15272

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