The H163A mutation unravels an oxidized conformation of the SARS-CoV-2 main protease.

The main protease of SARS-CoV-2 (Mpro) is an important target for developing COVID-19 therapeutics. Recent work has highlighted Mpro's susceptibility to undergo redox-associated conformational changes in response to cellular and immune-system-induced oxidation. Despite structural evidence indicating large-scale rearrangements upon oxidation, the mechanisms of conformational change and its functional consequences are poorly understood.

Cohesiveness and Nondiffusive Rotational Jump Dynamics of Protic Ionic Liquid from Dispersion-Corrected FPMD Simulations.

We have investigated the liquid phase of an ionic liquid (IL), methylammonium formate (MAF), through the first principles molecular dynamics simulations using van der Waals (vdW) corrected exchange and correlation functionals of the density functional theory. The simulations were carried out to obtain a comparative study of various properties of the MAF using two different generalized gradient approximation functionals (Becke-Lee-Yang-Parr (BLYP) and Perdew-Burke-Ernzerhof (PBE)) along with three types of dispersion corrections (D2, D3, and dispersion-corrected atom-centered one-electron potentials), and two values of the plane-wave cutoff (300 and 600 Ry). We have evaluated the effects of various electronic parameters in describing the hydrogen-bonded structure and dynamical properties of MAF by performing 10 sets of molecular dynamics simulations.

Conformational dynamics of amyloid-β (16-22) peptide in aqueous ionic liquids.

Molecular dynamics simulations of amyloid-β (16-22) peptide dimer in water as well as at two different experimentally studied concentrations of hydrated ionic liquids (ILs), ethylammonium mesylate (EAM), ethylammonium nitrate (EAN), and triethylammonium mesylate (TEAM), were carried out employing an umbrella sampling method. We used the average angle of the peptide backbone as the reaction coordinate to observe the conformational changes of a peptide dimer. Secondary structural element values were calculated for the peptide dimer along the reaction coordinate to see the transition of the peptide dimer between β-sheet and α-helix conformations.

Conformational Free-Energy Landscapes of Alanine Dipeptide in Hydrated Ionic Liquids from Enhanced Sampling Methods.

Understanding the interaction of the ionic liquid (IL) with protein is vital to find the origin of the conformational changes of proteins in these alternative solvents. Here, we performed biased molecular dynamics simulations of alanine dipeptide (ADP), a widely used model for protein backbone structure, in water and two hydrated ionic liquids (ILs): 80% (w/w) 1-ethyl-3-methylimidazolium acetate ([EMIm][Ac]) and 80% (w/w) choline dihydrogen phosphate ([Cho][DHP]). We employed three different biasing methods, metadynamics (metaD), well-tempered metadynamics (WT-metaD), and adaptive biasing force (ABF), to construct the free-energy landscapes of the ADP conformations using the backbone dihedral angles (ϕ and ψ) as the collective variables.

Thermophysical Properties and Angular Jump Dynamics of Water: A Comparative DFT and DFT-Dispersion-Based Molecular Dynamics Study.

We present the first-principles molecular dynamics simulations of water molecules using two different levels of density functional theory within the Kohn-Sham scheme, namely, Becke-Lee-Yang-Parr (BLYP) and Perdew-Burke-Ernzerhof (PBE) with dispersion corrections such as D2 as well as D3 versions of Grimme dispersion correction and dispersion-corrected atom-centered potential. Our aim is to provide a comparative study of these functionals in explaining the thermophysical and structural properties along with nondiffusive jump dynamics of water molecules concerning the experimental data. The hydrogen bonding phenomenon is dependent on polarity, bonding, as well as nonbonding interactions, which requires thorough parametrization.

Biosolvation Nature of Ionic Liquids: Molecular Dynamics Simulation of Methylated Nucleobases in Hydrated 1-Ethyl-3-methylimidazolium Acetate.

Solvation free energies of methylated nucleobases were calculated in pure and hydrated 1-ethyl-3-methylimidazolium acetate, [Emim][Ac], ionic liquid, and pure water using classical molecular dynamics simulations using multistate Bennett's acceptance ratio method. The calculated solvation free energies in pure water were compared with the previous experimental and theoretical findings and found to be in agreement. We observe that the solvation free energy of methylated nucleobases is more in the pure ionic liquid compared to that in the pure water and on changing the mole fraction of water in the ionic liquid, the solvation free energy decreases gradually.

Nondiffusive Rotational Jump Dynamics in Ethyl Ammonium Nitrate.

We examine the hydrogen bond jump mechanism in ionic liquid, ethyl ammonium nitrate (EAN), using classical molecular dynamics simulations. Hydrogen bond jump in EAN can occur through two different nondiffusive rotational jump mechanisms: N-H bond of ethyl ammonium can switch its hydrogen bond between two oxygen atoms of the same nitrate ion or it can break its hydrogen bond with the oxygen of a nitrate ion to form a new hydrogen bond with the oxygen atom of another nitrate ion. We observe the average magnitude of the jump angle of 30° in the first mechanism, whereas the jump angle for the second mechanism is 70°.

Association of Nucleobases in Hydrated Ionic Liquid from Biased Molecular Dynamics Simulations.

We employed metadynamics-based classical molecular dynamics simulations to methylated adenine-thymine (mA-mT) and guanine-cytosine (mG-mC) base pairs to see favorable conformations in various concentrations of hydrated 1-ethyl, 3-methyl imidazolium acetate. We investigated various stacked and hydrogen-bonded conformations of association of base pairs through appropriately chosen collective variables. Stacked conformations more favored in water for both base pairs, whereas Watson-Crick (WC) hydrogen-bonding conformations are favored in pure and hydrated ionic liquids (ILs) except for 0.

Hopping-mediated anion transport through a mannitol-based rosette ion channel.

Artificial anion selective ion channels with single-file multiple anion-recognition sites are rare. Here, we have designed, by hypothesis, a small molecule that self-organizes to form a barrel rosette ion channel in the lipid membrane environment. Being amphiphilic in nature, this molecule forms nanotubes through intermolecular hydrogen bond formation, while its hydrophobic counterpart is stabilized by hydrophobic interactions in the membrane.