Multiscale modeling of unfolding and bond dissociation of rubredoxin metalloprotein.

Mechanical properties of proteins that have a crucial effect on their operation. This study used a molecular dynamics simulation package to investigate rubredoxin unfolding on the atomic scale. Different simulation techniques were applied, and due to the dissociation of covalent/hydrogen bonds, this protein demonstrates several intermediate states in force-extension behavior. A conceptual model based on the cohesive finite element method was developed to consider the intermediate damages that occur during unfolding. This model is based on force-displacement curves derived from molecular dynamics results. The proposed conceptual model is designed to accurately identify bond rupture points and determine the associated forces. This is achieved by conducting a thorough comparison between molecular dynamics and cohesive finite element results. The utilization of a viscoelastic cohesive zone model allows for the consideration of loading rate effects. This rate-dependent model can be further developed and integrated into the multiscale modeling of large assemblies of metalloproteins, providing a comprehensive understanding of mechanical behavior while maintaining a reduced computational cost.

Unraveling Flow Separation at the Water-Carbon Nanotube Interface: An Atomic-Scale Overview by Molecular Dynamics Simulation.

Flow separation near the fluid-solid surface has attracted attention for decades. It is critical to understand the behavior of separated flow adjacent to the solid walls to broaden its range of potential applications. Therefore, we conducted molecular dynamics investigations to consider water flow separation at the water-carbon nanotube (CNT) interface for different diameters of CNTs between 13 and 50 Å and different pressures of 0.1-1.254 GPa. Density heat maps indicated that water flow separation is observed for all CNTs under high pressures, and an empty space of water molecules or evacuation is formed behind the CNTs. It is shown that in CNTs with small diameters, (10, 10) and (20, 20), the structure of the first layer (FL) of water molecules or hydrated layer adjacent to the CNT wall is completely preserved, indicating that evacuation occurs from behind the CNTs. In (30, 30) and (40, 40) CNTs, flow separation occurred from the FL of water molecules near the solid surface, and the layered structure of water around CNTs is completely destroyed. Our findings of fluid-solid and fluid-fluid interaction energies suggested that the flow separation can be due to an attraction between the FL of water molecules and CNT and a repulsion between the water molecules in the hydrated layer and the outer layers. Moreover, analyzing the relationship between the CNT size and flow separation revealed that in the case of small CNTs, there are extra water molecules that contribute to the structural stability of the hydrated layer by strengthening the repulsive interaction in the liquid-liquid surface.

Determinative factors in inhibition of aquaporin by different pharmaceuticals: Atomic scale overview by molecular dynamics simulation.

The inhibition of water permeation through aquaporins by ligands of pharmaceutical compounds is considered as a method to control the cell lifetime. The inhibition of aquaporin 1 (AQP1) by bacopaside-I and torsemide, was explored and its atomistic nature was elucidated by molecular docking and molecular dynamics (MD) simulation collectively along with Poisson-Boltzmann surface area (PBSA) method. Docking results revealed that torsemide has a lower level of docking energy in comparison with bacopaside-I at the cytoplasmic side. Furthermore, the effect of steric constraints on water permeation was accentuated. Bacopaside-I inhibits the channel properly due to the strong interaction with the channel and larger spatial volume, whereas torsemide blocks the cytoplasmic side of the channel imperfectly. The most probable active sites of AQP1 for the formation of hydrogen bonds between the inhibitor and the channel were identified by numerical analysis of the bonds. Eventually, free energy assessments indicate that binding of both inhibitors is favorable in complex with AQP1, and van der Waals interaction has an important contribution in stabilizing the complexes.