by Keyword: Viruses
Martí, Didac, Alemán, Carlos, Ainsley, Jon, Ahumada, Oscar, Torras, Juan, (2022). IgG1-b12–HIV-gp120 Interface in Solution: A Computational Study Journal Of Chemical Information And Modeling 62, 359-371
The use of broadly neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) has been shown to be a promising therapeutic modality in the prevention of HIV infection. Understanding the b12-gp120 binding mechanism under physiological conditions may assist the development of more broadly effective antibodies. In this work, the main conformations and interactions between the receptor-binding domain (RBD) of spike glycoprotein gp120 of HIV-1 and the IgG1-b12 mAb are studied. Accelerated molecular dynamics (aMD) and ab initio hybrid molecular dynamics have been combined to determine the most persistent interactions between the most populated conformations of the antibody-antigen complex under physiological conditions. The results show the most persistent receptor-binding mapping in the conformations of the antibody-antigen interface in solution. The binding-free-energy decomposition reveals a small enhancement in the contribution played by the CDR-H3 region to the b12-gp120 interface compared to the crystal structure.
JTD Keywords: antibody, complex, functionals, gp120 envelope glycoprotein, hiv, immunodeficiency-virus, noncovalent interactions, simulations, software integration, Ab initio, Accelerated molecular dynamics, Accelerated molecular-dynamics, Antibodies, Antigens, Binding energy, Binding mechanisms, Computational studies, Crystal structure, Diseases, Free energy, Hiv infection, Human immunodeficiency virus, Molecular dynamics, Neutralizing antibodies, Physiological condition, Physiology, Receptor-binding domains, Therapeutic modality, Viruses
Martí D, Torras J, Bertran O, Turon P, Alemán C, (2021). Temperature effect on the SARS-CoV-2: A molecular dynamics study of the spike homotrimeric glycoprotein Computational And Structural Biotechnology Journal 19, 1848-1862
Rapid spread of SARS-CoV-2 virus have boosted the need of knowledge about inactivation mechanisms to minimize the impact of COVID-19 pandemic. Recent studies have shown that SARS-CoV-2 virus can be disabled by heating, the exposure time for total inactivation depending on the reached temperature (e.g. more than 45 min at 329 K or less than 5 min at 373 K. In spite of recent crystallographic structures, little is known about the molecular changes induced by the temperature. Here, we unravel the molecular basis of the effect of the temperature over the SARS-CoV-2 spike glycoprotein, which is a homotrimer with three identical monomers, by executing atomistic molecular dynamics (MD) simulations at 298, 310, 324, 338, 358 and 373 K. Furthermore, both the closed down and open up conformational states, which affect the accessibility of receptor binding domain, have been considered. Our results suggest that the spike homotrimer undergoes drastic changes in the topology of the hydrogen bonding interactions and important changes on the secondary structure of the receptor binding domain (RBD), while electrostatic interactions (i.e. salt bridges) are mainly preserved. The proposed inactivation mechanism has important implications for engineering new approaches to fight the SARS-CoV-2 coronavirus, as for example, cleaving or reorganizing the hydrogen bonds through chaotropic agents or nanoparticles with local surface resonant plasmon effect.
JTD Keywords: atomistic simulations, coronaviruses, denaturation, homotrimeric protein, inactivation, proteins, receptor binding domain, salt bridges, simulation, thermal inactivation, virus spike, Atomistic simulations, Homotrimeric protein, Receptor binding domain, Secondary-structure, Thermal inactivation, Virus spike
Marti, D, Martin-Martinez, E, Torras, J, Bertran, O, Turon, P, Aleman, C, (2021). In silico antibody engineering for SARS-CoV-2 detection Computational And Structural Biotechnology Journal 19, 5525-5534
Engineered immunoglobulin-G molecules (IgGs) are of wide interest for the development of detection elements in protein-based biosensors with clinical applications. The strategy usually employed for the de novo design of such engineered IgGs consists on merging fragments of the three-dimensional structure of a native IgG, which is immobilized on the biosensor surface, and of an antibody with an exquisite target specificity and affinity. In this work conventional and accelerated classical molecular dynamics (cMD and aMD, respectively) simulations have been used to propose two IgG-like antibodies for COVID-19 detection. More specifically, the crystal structure of the IgG1 B12 antibody, which inactivates the human immunodeficiency virus-1, has been merged with the structure of the antibody CR3022 Fab tightly bounded to SARS-CoV-2 receptor-binding domain (RBD) and the structure of the 5309 antibody Fab fragment complexed with SARS-CoV-2 RBD. The two constructed antibodies, named IgG1-CR3022 and IgG1-S309, respectively, have been immobilized on a stable gold surface through a linker. Analyses of the influence of both the merging strategy and the substrate on the stability of the two constructs indicate that the IgG1-S309 antibody better preserves the neutralizing structure than the IgG1-CR3022 one. Overall, results indicate that the IgG1-S309 is appropriated for the generation of antibody based sensors for COVID-19 diagnosis. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
JTD Keywords: cr3022, igg1, molecular engineering, s309, Antibodies, Antibody engineering, Biosensors, Chemical detection, Clinical application, Cov, Cr3022, Crystal structure, Design, Diseases, Gold nanoparticles, Igg1, Igg1 antibody, Immobilization, Immunoglobulin g, Immunosensor, In-silico, Merging, Molecular dynamics, Molecular engineering, Orientation, Protein-based biosensors, Receptor-binding domains, S309, Sars, Sensor, Spike protein, Target, Vaccine, Viruses
Rahman, Abdel, Ganesh, Swapnil, Torrents, Eduard, Jahan, Nusrat, Wedyan, Moh'd Ali, Qaisi, Ali M., Al-Tawaha, Abdelrazzaq, (2020). Algal viruses Applied Plant Virology (ed. Awasthi, L. P.), Academic Press (London, UK) Advances, Detection, and Antiviral Strategies, 237-246
In marine ecosystems, the algae community is abundant and plays an important role in the food web. On the other hand, algal viruses have different advantages and disadvantages depending on the properties, such as applications of algal viruses in the advancement of molecular biology and for enhancement of biofuel production. Many environmental factors affecting growth and development of algae and virus such as temperature, salinity, ultraviolet radiation, photosynthetic active radiation, nutrients, inorganic particles, organic particles, CO2 concentration, and pH.
JTD Keywords: Algal viruses, Biofuel production, Nutrients
Sánchez-Martín, M. J., Urbán, P., Pujol, M., Haro, I., Alsina, M. A., Busquets, M. A., (2011). Biophysical investigations of GBV-C E1 peptides as potential inhibitors of HIV-1 fusion peptide ChemPhysChem , 12, (15), 2816-2822
Five peptide sequences corresponding to the E1 protein of GBV-C [NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCLVALGCTICTD (P10), QAGLAVRPGKSAAQLVGE (P18), and AQLVGELGSLYGPLSVSA (P22)] were synthesized because they were capable of interfering with the HIV-1 fusion peptide (HIV-1 FP)-vesicle interaction. In this work the interaction of these peptides with the HIV-1 FP, as well as with membrane models, was analyzed to corroborate their inhibition ability and to understand if the interaction with the fusion peptide takes place in solution or at the membrane level. Several studies were carried out on aggregation and membrane fusion, surface Plasmon resonance, and conformational analysis by circular dichroism. Moreover, in vitro toxicity assays, including cytotoxicity studies in 3T3 fibroblasts and hemolysis assays in human red blood cells, were performed to evaluate if these peptides could be potentially used in anti-HIV-1 therapy. Results show that P10 is not capable of inhibiting membrane fusion caused by HIV-1 and it aggregates liposomes and fuses membranes, thus we decided to discard it for futures studies. P18 and P22 do not inhibit membrane fusion, but they inhibit the ability of HIV-1 FP to form pores in bilayers, thus we have not discarded them yet. P7 and P8 were selected as the best candidates for future studies because they are capable of inhibiting membrane fusion and the interaction of HIV-1 FP with bilayers. Therefore, these peptides could be potentially used in future anti-HIV-1 research. Part of the gang: Liposomes are deposited on a surface plasmon resonance chip (see AFM image of the chip) to observe the interaction of peptides corresponding to the E1 envelop protein of the hepatitis G virus with membranes to show how they reduce the interaction of the HIV-1 fusion peptide.
JTD Keywords: HIV-1 fusion protein, Liposomes, Membranes, Peptides, Viruses