title: Investigating the effects of point mutations on the affinity between the cyanobacterial lectin microvirin and high mannose-type glycans present on the HIV envelope glycoprotein.
abstract: Human immunodeficiency virus (HIV) infections continue to exert an enormous impact on global human health. This led experts to emphasize the importance of new measures for preventing HIV infections, including the development of vaccines and novel drugs. In this context, a promising approach involves the use of lectins that can bind the surface envelope glycoprotein gp120 of HIV with high affinity, preventing viral entry. The cyanobacterial lectin microvirin (MVN) has been proposed as a candidate for development as a topical microbicide because of its ability to bind to high mannose-type glycans, potently inhibiting HIV-1 entry. Thus, the aim of this computational study was to investigate the effects of four point mutations (D53Q, D53E, D53K, and D53W) on the structure and affinity of MVN with di-mannose (MAN). Molecular dynamics simulations followed by binding free energy calculations using MM-GBSA were employed. The calculated binding free energy of ligand-receptor complexation of MVN with MAN was -26.02 kcal mol-1. We identified in the wild-type protein that residues I45, T59, and Q81 have a major contribution to the binding free energy of di-mannose. Among the investigated mutants, the most promising one was the D53W mutation, with a theoretical binding free energy value of -29.16 kcal mol-1. We suggest that this increased stability is due to the introduction of extra rigidity on the hinge region connecting two key structural elements of the MVN binding site.
authors: Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA, 67030-000, Brazil.|Faculdade Integrada Brasil Amazônia (FIBRA), Belém, PA, Brazil.
authors: Rafael
authors: R
authors: Conceição de Souza
authors: Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA, 67030-000, Brazil.
authors: Gabriela
authors: G
authors: de Medeiros Muniz
authors: Faculdade Integrada Brasil Amazônia (FIBRA), Belém, PA, Brazil.|Laboratório de Tecnologia Biomolecular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.
authors: Andrei Santos
authors: AS
authors: Siqueira
authors: Laboratório de Tecnologia Biomolecular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.
authors: Adonis
authors: A
authors: de Melo Lima
authors: Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA, 67030-000, Brazil.
authors: Alessandra Pereira
authors: AP
authors: da Silva
authors: Laboratório de Tecnologia Biomolecular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.
authors: Evonnildo Costa
authors: EC
authors: Gonçalves
authors: Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA, 67030-000, Brazil. vianez.iec@gmail.com.
authors: João Lídio
authors: JL
authors: da Silva Gonçalves Vianez Júnior
mesh_terms: D019943:Amino Acid Substitution; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D001665:Binding Sites; D000458:Cyanobacteria / Q000737:chemistry*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000235:genetics; D015497:HIV-1 / Q000737:chemistry* / Q000235:genetics; D037601:Mannose-Binding Lectin / Q000737:chemistry* / Q000235:genetics; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D017354:Point Mutation
chemical_list: D001426:Bacterial Proteins; D015699:HIV Envelope Protein gp120; D037601:Mannose-Binding Lectin; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: Antiviral activity; Bind free energy; Lectin; Microvirin; Molecular dynamics