ORIGINAL PAPER 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 Rafael Conceição de Souza 1,2 & Gabriela de Medeiros Muniz 1 & Andrei Santos Siqueira 2,3 & Adonis de Melo Lima 3 & Alessandra Pereira da Silva 1 & Evonnildo Costa Gonçalves 3 & João Lídio da Silva Gonçalves Vianez Júnior 1 Received: 10 June 2016 /Accepted: 9 October 2016 # Springer-Verlag Berlin Heidelberg 2016 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 ap- proach 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 introduc- tion of extra rigidity on the hinge region connecting two key structural elements of the MVN binding site. Keywords Antiviral activity . Bind free energy . Lectin . Microvirin . Molecular dynamics Introduction Infection by human immunodeficiency virus (HIV) con- tinues to exert a huge global human health problem, caus- ing about 25 million deaths per year worldwide [1, 2]. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS: www.unaids.org), in 2014, 36.9 million people were living with HIV and this number continues to increase. In the same year, about 2 million people were infected with HIV and 1.2 million people died of AIDS-related diseases [3]. Currently, prevention options are not practical for millions of people around the world, moreover, despite the advance in the therapies with anti-retroviral drugs which can extend the life expectancy of patients infected with HIV, the disparate access to med- ications and resistance to anti-HIV approved drugs could compromise the results [4]. Thus, there is an urgent need to develop new methods of prevention against HIV. The HIV-infection process begins with the adhesion of the virus to the host cell, resulting in the fusion of the viral and cell membranes. One key step to this fusion process is the specific recognition between the gp120 and gp41 glycoproteins present in the viral envelope and the cellular receptor CD4, and subsequently to the co- receptors CCR5 and/or CXCR4. Both gp120 and gp41 Electronic supplementary material The online version of this article (doi:10.1007/s00894-016-3137-3) contains supplementary material, which is available to authorized users. * João Lídio da Silva Gonçalves Vianez Júnior vianez.iec@gmail.com 1 Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA 67030-000, Brazil 2 Faculdade Integrada Brasil Amazônia (FIBRA), Belém, PA, Brazil 3 Laboratório de Tecnologia Biomolecular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil J Mol Model (2016) 22:269 DOI 10.1007/s00894-016-3137-3