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Energetic and structural basis for the differences in infectivity between the wild-type and mutant spike proteins of SARS-CoV-2 in the Mexican population.
J Mol Graph Model. 2021 09; 107:107970.JM

Abstract

SARS-CoV-2 is the causative agent of the ongoing viral pandemic of COVID-19. After the emergence of this virus, it became a global public health concern and quickly evolved into a pandemic. Mexico is currently in the third position in the number of deaths due to SARS-CoV-2. To date, there have been several lineages of SARS-CoV-2 worldwide; in the Mexican population, two variants of the spike protein (S-protein) are found, localized at H49Y and D614G, which have been related to increased infectivity with respect to the wild-type S-protein. To understand how these differences impact the structural behavior of the S-protein of SARS-CoV-2, as well as binding with ACE2, we performed MD simulations combined with the molecular mechanics generalized Born/Poisson-Boltzmann surface area (MMGB(PB)SA) approach starting from X-ray crystallography data. Energetic and structural analysis showed that the differences in infectivity can be explained by differences in affinity of the protein-protein interface between the wild-type and mutant S-protein with ACE2. Conformational analysis showed that molecular recognition between the S-protein and ACE2 is linked to a decrease in the conformational flexibility of wild-type and mutant S-protein; however, an increase in the conformational mobility of ACE2 could also contribute to the binding affinity observed using the MMGB(PB)SA method.

Authors+Show Affiliations

Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica de la Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico. Electronic address: bellomartini@gmail.com.Department of Biochemistry and Molecular Biology, Tejgaon College, National University, Gazipur, 1704, Bangladesh.Department of Biochemistry and Molecular Biology, Tejgaon College, National University, Gazipur, 1704, Bangladesh.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34242876

Citation

Bello, Martiniano, et al. "Energetic and Structural Basis for the Differences in Infectivity Between the Wild-type and Mutant Spike Proteins of SARS-CoV-2 in the Mexican Population." Journal of Molecular Graphics & Modelling, vol. 107, 2021, p. 107970.
Bello M, Hasan MK, Hussain N. Energetic and structural basis for the differences in infectivity between the wild-type and mutant spike proteins of SARS-CoV-2 in the Mexican population. J Mol Graph Model. 2021;107:107970.
Bello, M., Hasan, M. K., & Hussain, N. (2021). Energetic and structural basis for the differences in infectivity between the wild-type and mutant spike proteins of SARS-CoV-2 in the Mexican population. Journal of Molecular Graphics & Modelling, 107, 107970. https://doi.org/10.1016/j.jmgm.2021.107970
Bello M, Hasan MK, Hussain N. Energetic and Structural Basis for the Differences in Infectivity Between the Wild-type and Mutant Spike Proteins of SARS-CoV-2 in the Mexican Population. J Mol Graph Model. 2021;107:107970. PubMed PMID: 34242876.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Energetic and structural basis for the differences in infectivity between the wild-type and mutant spike proteins of SARS-CoV-2 in the Mexican population. AU - Bello,Martiniano, AU - Hasan,Md Kamrul, AU - Hussain,Nazmul, Y1 - 2021/06/17/ PY - 2021/03/09/received PY - 2021/05/02/revised PY - 2021/06/10/accepted PY - 2021/7/10/pubmed PY - 2021/7/31/medline PY - 2021/7/9/entrez KW - Binding free energy KW - COVID-19 KW - Molecular dynamics simulation KW - SARS-CoV-2 KW - Spike protein SP - 107970 EP - 107970 JF - Journal of molecular graphics & modelling JO - J Mol Graph Model VL - 107 N2 - SARS-CoV-2 is the causative agent of the ongoing viral pandemic of COVID-19. After the emergence of this virus, it became a global public health concern and quickly evolved into a pandemic. Mexico is currently in the third position in the number of deaths due to SARS-CoV-2. To date, there have been several lineages of SARS-CoV-2 worldwide; in the Mexican population, two variants of the spike protein (S-protein) are found, localized at H49Y and D614G, which have been related to increased infectivity with respect to the wild-type S-protein. To understand how these differences impact the structural behavior of the S-protein of SARS-CoV-2, as well as binding with ACE2, we performed MD simulations combined with the molecular mechanics generalized Born/Poisson-Boltzmann surface area (MMGB(PB)SA) approach starting from X-ray crystallography data. Energetic and structural analysis showed that the differences in infectivity can be explained by differences in affinity of the protein-protein interface between the wild-type and mutant S-protein with ACE2. Conformational analysis showed that molecular recognition between the S-protein and ACE2 is linked to a decrease in the conformational flexibility of wild-type and mutant S-protein; however, an increase in the conformational mobility of ACE2 could also contribute to the binding affinity observed using the MMGB(PB)SA method. SN - 1873-4243 UR - https://www.unboundmedicine.com/medline/citation/34242876/Energetic_and_structural_basis_for_the_differences_in_infectivity_between_the_wild_type_and_mutant_spike_proteins_of_SARS_CoV_2_in_the_Mexican_population_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1093-3263(21)00141-8 DB - PRIME DP - Unbound Medicine ER -