Biology subjects

de Araujo, A. S.

Publications and source records attributed to de Araujo, A. S..

2 recordsLinked to original sources

bioRxiv2025

Synergistic Effects of pH and Temperature on Dengue VirusEnvelope Dimers: Insights from Microsecond MolecularDynamics Simulations

Dengue pathogenesis depends on a conformational rearrangement of the envelope (E) glycoprotein induced by low pH; however, how pH and temperature cooperate to destabilize its prefusion dimeric state, a fundamental step that enables the formation of the fusion-active trimer, remains unclear. Here, we investigate this synergy for Dengue serotypes of greatest medical relevance, DENV-2 and DENV-3. All-atom molecular dynamics simulations were performed on the microsecond scale, at 28 {degrees}C, 37 {degrees}C, and 40 {degrees}C under pH 5-7, using CHARMM36m force fields. The increase in temperature from 28 {degrees}C to 37 {degrees}C doubled the conformational space explored at neutral pH and weakened both dimers through the reduction or loss of the interaction network along the dimeric interface. Acidification amplified this effect in a serotype-specific manner: DENV-2 required pH 5, while DENV-3 responded at pH 6. Distance and principal component analyses revealed an asymmetric dissociation route, termed the "compensatory embrace", in which retraction of Domains I and III in one monomer is balanced by advancement of its partner on the opposite side, temporarily preserving the number of inter-subunit contacts. Structural analyses highlighted the difference in histidine distribution between the serotypes. These results outline hierarchical physicochemical triggers that convert the dimer into fusion-competent monomers. Targeting the interfacial interaction network or reinforcing the "compensatory embrace" to prevent completion of dissociation offers new perspectives for broad-spectrum antivirals and immunogen design, underscoring the value of long-timescale molecular dynamics in drug discovery.

biophysics↗

bioRxiv2021

A method for detection of permeation events in Molecular Dynamics simulations of lipid bilayers

The cell membrane is one of the most important structures of life. Understanding its functioning is essential for several human knowledge areas, mainly how it controls the efflux of substances between the cytoplasm and the environment. Being a complex structure, composed of several classes of compounds such as lipids, proteins, sugars, etc., a convenient way to mimic it is through a phospholipid bilayer. The Molecular Dynamics simulation of lipid bilayers in solution is the main computational approach to model the cell membrane. In this work, we present a method to detect permeation events of molecules through the lipid bilayer, characterizing its crossing time and trajectory. By splitting the simulation box into well-defined regions, the method distinguishes the passage of molecules through the bilayer from artifacts produced by crossing molecules through the simulation box edges when using periodic boundary conditions. We apply the method to study the spontaneous permeation of water molecules through bilayers with different lipid compositions and modeled with different force fields. Our method successfully characterizes the permeation events, and the results obtained show that the frequency and time of permeation are independent of the force field used to model the phospholipids. Besides, it is observed that the increase in the concentration of cholesterol molecules in lipid bilayers induces the reduction of permeation events due to its compacting action on the bilayer, making it denser and, therefore, hindering the diffusion of water molecules inside it. The computational tool to perform the method discussed here is available on https://github.com/crobertocamilo/MD-permeation.

bioinformatics↗