Biology subjects

Monje-Galvan, V.

Publications and source records attributed to Monje-Galvan, V..

3 recordsLinked to original sources

bioRxiv2021

Molecular interactions of the M and E integral membrane proteins of SARS-CoV-2

Specific lipid-protein interactions are key for cellular processes, and even more so for the replication of pathogens. The COVID-19 pandemic has drastically changed our lives and cause the death of nearly three million people worldwide, as of this writing. SARS-CoV-2 is the virus that causes the disease and has been at the center of scientific research over the past year. Most of the research on the virus is focused on key players during its initial attack and entry into the cellular host; namely the S protein, its glycan shield, and its interactions with the ACE2 receptors of human cells. As cases continue to raise around the globe, and new mutants are identified, there is an urgent need to understand the mechanisms of this virus during different stages of its life cycle. Here, we consider two integral membrane proteins of SARS-CoV-2 known to be important for viral assembly and infectivity. We have used microsecond-long all-atom molecular dynamics to examine the lipid-protein and protein-protein interactions of the membrane (M) and envelope (E) structural proteins of SARS-CoV-2 in a complex membrane model. We contrast the two proposed protein complexes for each of these proteins, and quantify their effect on their local lipid environment. This ongoing work also aims to provide molecular-level understanding of the mechanisms of action of this virus to possibly aid in the design of novel treatments.

biophysics↗

bioRxiv2020

A Multiscale Coarse-grained Model of the SARS-CoV-2 Virion

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Computer simulations of complete viral particles can provide theoretical insights into large-scale viral processes including assembly, budding, egress, entry, and fusion. Detailed atomistic simulations, however, are constrained to shorter timescales and require billion-atom simulations for these processes. Here, we report the current status and on-going development of a largely "bottom-up" coarse-grained (CG) model of the SARS-CoV-2 virion. Structural data from a combination of cryo-electron microscopy (cryo-EM), x-ray crystallography, and computational predictions were used to build molecular models of structural SARS-CoV-2 proteins, which were then assembled into a complete virion model. We describe how CG molecular interactions can be derived from all-atom simulations, how viral behavior difficult to capture in atomistic simulations can be incorporated into the CG models, and how the CG models can be iteratively improved as new data becomes publicly available. Our initial CG model and the detailed methods presented are intended to serve as a resource for researchers working on COVID-19 who are interested in performing multiscale simulations of the SARS-CoV-2 virion. Significance StatementThis study reports the construction of a molecular model for the SARS-CoV-2 virion and details our multiscale approach towards model refinement. The resulting model and methods can be applied to and enable the simulation of SARS-CoV-2 virions.

biophysics↗

bioRxiv2020

Binding Mechanism of the Matrix Domain of HIV-1 Gag to Lipid Membranes

Aggregation of the HIV-1 Gag protein onto the plasma membrane (PM) enables viral budding and infection propagation. Gag assembly at the membrane interface is mediated by its matrix domain (MA), the Myristoylated (Myr) N-terminus. MA targets the PM through electrostatic interactions, mainly at its highly-basic-region (HBR). The mechanism of Myr insertion and its role in protein-membrane dynamics remains unclear. Using all-atom molecular dynamics, we examined an MA unit in the vicinity of lipid bilayers that model different characteristics of the PM. Interaction with PIP2 and PS lipids is highly favored around the HBR, and is enough to keep the protein bound. Additionally, we simulated three MA units near our bilayers and quantified the collective effects of free monomers vs. formed trimers on Myr insertion events. Micro-second-long trajectories allowed us to observe Myr insertion, propose a mechanism, quantify specific interactions with lipids, and examine the response of the local membrane environment.

biophysics↗