In Silico Prediction and Molecular Docking of SNPs in NRP1 Gene Associated with SARS-COV-2

• Published in: Biochemical genetics Vol. 62; no. 1; pp. 156 - 175
• Main Authors: Özkan Oktay, Ebru, Kaman, Tuğba, Karasakal, Ömer Faruk, Enisoğlu Atalay, Vildan
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-02-2024; Springer Nature B.V
• Subjects: Amino acids; Angiogenesis; Axonogenesis; Binding sites; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell surface; Cell surface receptors; Human Genetics; Hydrophobicity; Infectivity; Medical Microbiology; miRNA; Molecular docking; mRNA; Mutants; Mutation; Neuropilin; NRP1 gene; Nucleotides; Original; Original Article; Protein structure; Proteins; Severe acute respiratory syndrome coronavirus 2; Single-nucleotide polymorphism; Spike protein; Structure-function relationships; Zoology; Neuropilin-1; SARS-CoV-2; Single nucleotide polymorphism (SNP); In silico analysis; Neuropilin-1 (NRP1)
• DOI: 10.1007/s10528-023-10409-6
• EISSN: 1573-4927
• ISSN: 0006-2928

Neuropilin-1 (NRP1) which is a main transmembrane cell surface receptor acts as a host cell mediator resulting in increasing the SARS-Cov-2 infectivity and also plays a role in neuronal development, angiogenesis and axonal outgrowth. The goal of this study is to estimate the impact of single nucleotide polymorphisms (SNPs) in the
NRP1
gene on the function, structure and stabilization of protein as well as on the miRNA-mRNA binding regions using bioinformatical tools. It is also aimed to investigate the changes caused by SNPs in NRP1 on interactions with drug molecule and spike protein. The missense type of SNPs was analyzed using SIFT, PolyPhen-2, SNAP2, PROVEAN, Mutation Assessor, SNPs&GO, PhD-SNP, I-Mutant 3.0, MUpro, STRING, Project HOPE, ConSurf, and PolymiRTS. Docking analyses were conducted by AutoDock Vina program. As a result, a total of 733 missense SNPs were determined within the
NRP1
gene and nine SNPs were specified as damaging to the protein. The modelling results showed that wild and mutant type amino acids had some different properties such as size, charge, and hydrophobicity. Additionally, their three-dimensional structures of protein were utilized for confirmation of these differences. After evaluating the results, nine polymorphisms rs141633354, rs142121081, rs145954532, rs200028992, rs200660300, rs369312020, rs370117610, rs370551432, rs370641686 were determined to be damaging on the structure and function of NRP1 protein and located in conserved regions. The results of molecular docking showed that the binding affinity values are nearly the same for wild-type and mutant structures support that the mutations carried out are not in the focus of the binding site, therefore the ligand does not affect the binding energy. It is expected that the results will be useful for future studies.