Molecular Dynamics Study of Structure, Folding, and Aggregation of Poly-PR and Poly-GR Proteins

Discontinuous Molecular Dynamics Simulations of Biomolecule Interfacial Behavior: Study of Ovispirin-1 Adsorption on a Graphene Surface

“…Our DMD simulation code was also used to present protein folding in the bulk environment in several of our previous papers. 56,57,66 In this work, our simulations of ovispirin-1 peptide adsorption are in agreement with atomistic MD simulations. Moreover, we compared the simulated secondary structure of the peptide in the bulk environment with the solution structure (pdb code 1HWA) measured with an NMR experiment, 81 which further validated our DMD simulations (see Figure S1).…”

“…The simulations were started with energy minimization, followed by a series of short-runs that gradually increased the temperature from 0.4 to 0.57. At each temperature step, the system was relaxed for 2 × 10 4 timesteps, following the protocol published in our previous studies. − Then the production runs were carried out at the temperature of 0.57 in the NVT ensemble until the time step reached 2 × 10 6 . Each simulation took about 36 h to finish by serial computation on an AMD Ryzen 9 3900X clocked at 3.8 GHz.…”

“…Both coarse-grained − and atomistic models − have been adopted in DMD to study a complex biological system at large time and spatial scales, which are difficult for atomistic MD simulations to handle. We used DMD to successfully simulate the aggregation of polyalanines, the configuration of which is intended to mimic the hydrophobic part of β-amyloid, under bulk conditions and in a confined medium, and the aggregation of dipeptide repeat proteins , which are associated with amyotrophic lateral sclerosis and frontotemporal dementia. Those simulations, − which covered the whole dynamic process from ab initio to the final equilibrium state, cost shorter computational time compared with the conventional atomistic MD, and matched experimental measurements.…”

Endothelial metabolism in pulmonary vascular homeostasis and acute respiratory distress syndrome

“…High levels of compartmentalized ATP at AJs favor VE-cadherin internalization and activate NF-κB, permeabilizing the endothelial barrier ( 1 – 3 , 103 ). Depleted ATP content at the membrane impairs AJ dynamics and actin remodeling, disrupting normal barrier homeostasis ( 1 , 99 ). Optimal ATP content limits VE-cadherin internalization while retaining enough ATP to support AJ dynamics and actin remodeling, stabilizing the endothelial barrier.…”

“…Chemical inhibition of PFKFB3 with 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one (PFK15) destabilized AJs in human PMVECs by disrupting VE-cadherin recycling and global actin networks, increasing cell-cell gap formation and compromising the endothelial barrier ( 99 ). In opposition to this, treatment of human umbilical venous endothelial cells (HUVECs) with the PFKFB3 inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) blocked VE-cadherin endocytosis, leading to a tighter barrier with fewer gaps ( 2 ).…”