E-Volve: understanding the impact of mutations in SARS-CoV-2 variants spike protein on antibodies and ACE2 affinity through patterns of chemical interactions at protein interfaces.

Autor:	Dos Santos VP; Laboratory of Bioinformatics and Systems, Institute of Exact Sciences, Department of Computer Science, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Rodrigues A; Laboratory of Bioinformatics and Systems, Institute of Exact Sciences, Department of Computer Science, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Dutra G; Laboratory of Bioinformatics and Systems, Institute of Exact Sciences, Department of Computer Science, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Bastos L; Laboratory of Bioinformatics and Systems, Institute of Exact Sciences, Department of Computer Science, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Mariano D; Laboratory of Bioinformatics and Systems, Institute of Exact Sciences, Department of Computer Science, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Mendonça JG; Laboratory of Quantum and Computational Chemistry, Center of Exact and Natural Sciences, Department of Chemistry, Universidade Federal da Paraíba, João Pessoa, PB, Brazil., Lobo YJG; Laboratory of Molecular Modeling and Bioinformatics, Campus Sete Lagoas, Department of Exact and Biological Sciences, Universidade Federal de São João del-Rei, Sete Lagoas, MG, Brazil., Mendes E; Laboratory of Bioinformatics and Systems, Institute of Exact Sciences, Department of Computer Science, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Maia G; Laboratory of Bioinformatics and Systems, Institute of Exact Sciences, Department of Computer Science, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Machado KDS; Computational Biology Laboratory (ComBi-Lab), Center for Computational Sciences-C3, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil., Werhli AV; Computational Biology Laboratory (ComBi-Lab), Center for Computational Sciences-C3, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil., Rocha G; Laboratory of Quantum and Computational Chemistry, Center of Exact and Natural Sciences, Department of Chemistry, Universidade Federal da Paraíba, João Pessoa, PB, Brazil., de Lima LHF; Laboratory of Molecular Modeling and Bioinformatics, Campus Sete Lagoas, Department of Exact and Biological Sciences, Universidade Federal de São João del-Rei, Sete Lagoas, MG, Brazil., de Melo-Minardi R; Laboratory of Bioinformatics and Systems, Institute of Exact Sciences, Department of Computer Science, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Jazyk:	angličtina
Zdroj:	PeerJ [PeerJ] 2022 Mar 22; Vol. 10, pp. e13099. Date of Electronic Publication: 2022 Mar 22 (Print Publication: 2022).
DOI:	10.7717/peerj.13099
Abstrakt:	Background: The SARS-CoV-2 pandemic reverberated, posing health and social hygiene obstacles throughout the globe. Mutant lineages of the virus have concerned scientists because of convergent amino acid alterations, mainly on the viral spike protein. Studies have shown that mutants have diminished activity of neutralizing antibodies and enhanced affinity with its human cell receptor, the ACE2 protein. Methods: Hence, for real-time measuring of the impacts caused by variant strains in such complexes, we implemented E-Volve, a tool designed to model a structure with a list of mutations requested by users and return analyses of the variant protein. As a proof of concept, we scrutinized the spike-antibody and spike-ACE2 complexes formed in the variants of concern, B.1.1.7 (Alpha), B.1.351 (Beta), and P.1 (Gamma), by using contact maps depicting the interactions made amid them, along with heat maps to quantify these major interactions. Results: The results found in this study depict the highly frequent interface changes made by the entire set of mutations, mainly conducted by N501Y and E484K. In the spike-Antibody complex, we have noticed alterations concerning electrostatic surface complementarity, breaching essential sites in the P17 and BD-368-2 antibodies. Alongside, the spike-ACE2 complex has presented new hydrophobic bonds. Discussion: Molecular dynamics simulations followed by Poisson-Boltzmann calculations corroborate the higher complementarity to the receptor and lower to the antibodies for the K417T/E484K/N501Y (Gamma) mutant compared to the wild-type strain, as pointed by E-Volve, as well as an intensification of this effect by changes at the protein conformational equilibrium in solution. A local disorder of the loop α1'/β1', as well its possible effects on the affinity to the BD-368-2 antibody were also incorporated to the final conclusions after this analysis. Moreover, E-Volve can depict the main alterations in important biological structures, as shown in the SARS-CoV-2 complexes, marking a major step in the real-time tracking of the virus mutant lineages. E-Volve is available at http://bioinfo.dcc.ufmg.br/evolve. Competing Interests: The authors declare that they have no competing interests. (© 2022 Dos Santos et al.)
Databáze:	MEDLINE
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