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Investigation of nonsynonymous mutations in the spike protein of SARS-CoV-2 and its interaction with the ACE2 receptor by molecular docking and MM/GBSA approach.
Comput Biol Med. 2021 08; 135:104654.CB

Abstract

COVID-19 is an infectious and pathogenic viral disease caused by SARS-CoV-2 that leads to septic shock, coagulation dysfunction, and acute respiratory distress syndrome. The spreading rate of SARS-CoV-2 is higher than MERS-CoV and SARS-CoV. The receptor-binding domain (RBD) of the Spike-protein (S-protein) interacts with the human cells through the host angiotensin-converting enzyme 2 (ACE2) receptor. However, the molecular mechanism of pathological mutations of S-protein is still unclear. In this perspective, we investigated the impact of mutations in the S-protein and their interaction with the ACE2 receptor for SAR-CoV-2 viral infection. We examined the stability of pathological nonsynonymous mutations in the S-protein, and the binding behavior of the ACE2 receptor with the S-protein upon nonsynonymous mutations using the molecular docking and MM_GBSA approaches. Using the extensive bioinformatics pipeline, we screened the destabilizing (L8V, L8W, L18F, Y145H, M153T, F157S, G476S, L611F, A879S, C1247F, and C1254F) and stabilizing (H49Y, S50L, N501Y, D614G, A845V, and P1143L) nonsynonymous mutations in the S-protein. The docking and binding free energy (ddG) scores revealed that the stabilizing nonsynonymous mutations show increased interaction between the S-protein and the ACE2 receptor compared to native and destabilizing S-proteins and that they may have been responsible for the virulent high level. Further, the molecular dynamics simulation (MDS) approach reveals the structural transition of mutants (N501Y and D614G) S-protein. These insights might help researchers to understand the pathological mechanisms of the S-protein and provide clues regarding mutations in viral infection and disease propagation. Further, it helps researchers to develop an efficient treatment approach against this SARS-CoV-2 pandemic.

Authors+Show Affiliations

Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. Electronic address: raljindan@iau.edu.sa.Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. Electronic address: amnalsubaie@iau.edu.sa.Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. Electronic address: aalohali@iau.edu.sa.Meenakshi Academy of Higher Education and Research, Chennai, Tamil Nadu, 600078, India. Electronic address: thirumalkumar.d@gmail.com.School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India. Electronic address: georgepriyadoss@vit.ac.in.Department of Neuroscience Technology, College of Applied Medical Sciences in Jubail, Imam Abdulrahman Bin Faisal University, Jubail, Saudi Arabia. Electronic address: bkranganayaki@iau.edu.sa.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34346317

Citation

Aljindan, Reem Y., et al. "Investigation of Nonsynonymous Mutations in the Spike Protein of SARS-CoV-2 and Its Interaction With the ACE2 Receptor By Molecular Docking and MM/GBSA Approach." Computers in Biology and Medicine, vol. 135, 2021, p. 104654.
Aljindan RY, Al-Subaie AM, Al-Ohali AI, et al. Investigation of nonsynonymous mutations in the spike protein of SARS-CoV-2 and its interaction with the ACE2 receptor by molecular docking and MM/GBSA approach. Comput Biol Med. 2021;135:104654.
Aljindan, R. Y., Al-Subaie, A. M., Al-Ohali, A. I., Kumar D, T., Doss C, G. P., & Kamaraj, B. (2021). Investigation of nonsynonymous mutations in the spike protein of SARS-CoV-2 and its interaction with the ACE2 receptor by molecular docking and MM/GBSA approach. Computers in Biology and Medicine, 135, 104654. https://doi.org/10.1016/j.compbiomed.2021.104654
Aljindan RY, et al. Investigation of Nonsynonymous Mutations in the Spike Protein of SARS-CoV-2 and Its Interaction With the ACE2 Receptor By Molecular Docking and MM/GBSA Approach. Comput Biol Med. 2021;135:104654. PubMed PMID: 34346317.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigation of nonsynonymous mutations in the spike protein of SARS-CoV-2 and its interaction with the ACE2 receptor by molecular docking and MM/GBSA approach. AU - Aljindan,Reem Y, AU - Al-Subaie,Abeer M, AU - Al-Ohali,Ahoud I, AU - Kumar D,Thirumal, AU - Doss C,George Priya, AU - Kamaraj,Balu, Y1 - 2021/07/16/ PY - 2021/01/28/received PY - 2021/07/12/revised PY - 2021/07/13/accepted PY - 2021/8/5/pubmed PY - 2021/9/7/medline PY - 2021/8/4/entrez KW - ACE2 receptor KW - Binding affinity KW - Nonsynonymous mutations KW - SARS-CoV-2 KW - Spike protein KW - Stability SP - 104654 EP - 104654 JF - Computers in biology and medicine JO - Comput Biol Med VL - 135 N2 - COVID-19 is an infectious and pathogenic viral disease caused by SARS-CoV-2 that leads to septic shock, coagulation dysfunction, and acute respiratory distress syndrome. The spreading rate of SARS-CoV-2 is higher than MERS-CoV and SARS-CoV. The receptor-binding domain (RBD) of the Spike-protein (S-protein) interacts with the human cells through the host angiotensin-converting enzyme 2 (ACE2) receptor. However, the molecular mechanism of pathological mutations of S-protein is still unclear. In this perspective, we investigated the impact of mutations in the S-protein and their interaction with the ACE2 receptor for SAR-CoV-2 viral infection. We examined the stability of pathological nonsynonymous mutations in the S-protein, and the binding behavior of the ACE2 receptor with the S-protein upon nonsynonymous mutations using the molecular docking and MM_GBSA approaches. Using the extensive bioinformatics pipeline, we screened the destabilizing (L8V, L8W, L18F, Y145H, M153T, F157S, G476S, L611F, A879S, C1247F, and C1254F) and stabilizing (H49Y, S50L, N501Y, D614G, A845V, and P1143L) nonsynonymous mutations in the S-protein. The docking and binding free energy (ddG) scores revealed that the stabilizing nonsynonymous mutations show increased interaction between the S-protein and the ACE2 receptor compared to native and destabilizing S-proteins and that they may have been responsible for the virulent high level. Further, the molecular dynamics simulation (MDS) approach reveals the structural transition of mutants (N501Y and D614G) S-protein. These insights might help researchers to understand the pathological mechanisms of the S-protein and provide clues regarding mutations in viral infection and disease propagation. Further, it helps researchers to develop an efficient treatment approach against this SARS-CoV-2 pandemic. SN - 1879-0534 UR - https://www.unboundmedicine.com/medline/citation/34346317/Investigation_of_nonsynonymous_mutations_in_the_spike_protein_of_SARS_CoV_2_and_its_interaction_with_the_ACE2_receptor_by_molecular_docking_and_MM/GBSA_approach_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0010-4825(21)00448-0 DB - PRIME DP - Unbound Medicine ER -