Histidine Protonation States Regulate the State Transition from R State Hemoglobin.

The objective of our work is to investigate the impact of pH on the structural changes of hemoglobin that affect its O affinity, known as the Bohr effect. We conducted molecular dynamics (MD) simulations to explore the transition between various hemoglobin states based on the protonation states (PSs) of two histidine residues (βHis143 and βHis146). We conducted the MD simulations from the R and R2 states with three sets of PSs assuming pH values of 7.

Chloride Ions Stabilize Human Adult Hemoglobin in the T-State, Competing with Allosteric Interaction of Oxygen Molecules.

In the context of a molecular-level understanding of the allostery mechanisms, human adult hemoglobin (HbA) has been extensively studied for over half a century. Chloride ions (Cl) have been known as one of HbA allosteric effectors, which stabilizes the T-state preferable to release oxygen molecules. The functional mechanisms were individually proposed by Ueno and Perutz several decades ago.

A Constant-pH Hybrid Monte Carlo Method with a Configuration-Selection Scheme Using the Zero Energy Difference Condition: Elucidation of Molecular Diffusivity Correlated with a pH-Dependent Solvation Shell.

We have proposed a new constant-pH (CpH) hybrid Monte Carlo (MC) method with a configuration-selection (CS) scheme, called the CS-CpH method, to obtain pH-dependent physical properties within a framework of atomistic molecular simulation. The CS-CpH method consists of carrying out a short equilibrium molecular dynamics (MD) and a searching MD coupled with thermostats and barostats to generate physically plausible configurations with changed protonation states (PSs) that are subsequently accepted or rejected according to the Metropolis MC procedure. As an example, we have applied it to glutamic acid in aqueous solution and have demonstrated that it can work to generate reasonably the pH-dependent microscopic configuration ensemble compatible with the experimental p value and also to show interestingly the molecular diffusivity correlated with pH-dependent solvation shell.

Vibrational Spectroscopy in Solution through Perturbative ab Initio Molecular Dynamics Simulations.

We have developed a method that allows computing the vibrational spectra at a high quantum mechanical level for molecules in solution or other complex systems. The method is based on the use of configurational samplings from combined QM/MM molecular dynamics simulations and the use of perturbation theory to calculate accurate molecular properties. Such calculations provide in addition accurate free energy gradient vectors and Hessian matrices and thus open the door for the characterization of stationary points in free energy landscapes and the study of chemical reaction mechanisms in large disordered systems.

Microscopic Origin of Different Hydration Patterns of para-Nitrophenol and Its Anion: A Study Combining Multiconfigurational Calculations and the Free-Energy Gradient Method.

A theoretical study of the solvatochromic shifts of para-nitrophenol ( pNP) and para-nitrophenolate anion ( pNP) in aqueous solution is presented using a QM/MM methodology with molecular dynamics simulation. The optimized structures in aqueous solution are obtained using both the polarizable continuum and the free-energy gradient methods. For pNP, the calculated redshifts at the CASPT2 (12,10) level are, respectively, 0.

Cost-Effective Method for Free-Energy Minimization in Complex Systems with Elaborated Ab Initio Potentials.

We describe a method to locate stationary points in the free-energy hypersurface of complex molecular systems using high-level correlated ab initio potentials. In this work, we assume a combined QM/MM description of the system although generalization to full ab initio potentials or other theoretical schemes is straightforward. The free-energy gradient (FEG) is obtained as the mean force acting on relevant nuclei using a dual level strategy.

Efficient Computational Research Protocol to Survey Free Energy Surface for Solution Chemical Reaction in the QM/MM Framework: The FEG-ER Methodology and Its Application to Isomerization Reaction of Glycine in Aqueous Solution.

In solution chemical reaction, we often need to consider a multidimensional free energy (FE) surface (FES) which is analogous to a Born-Oppenheimer potential energy surface. To survey the FES, an efficient computational research protocol is proposed within the QM/MM framework; (i) we first obtain some stable states (or transition states) involved by optimizing their structures on the FES, in a stepwise fashion, finally using the free energy gradient (FEG) method, and then (ii) we directly obtain the FE differences among any arbitrary states on the FES, efficiently by employing the QM/MM method with energy representation (ER), i.e.

Dual Approach to Vibrational Spectra in Solution: Microscopic Influence of Hydrogen Bonding to the State of Motion of Glycine in Water.

We have proposed a new theoretical methodology to clarify the microscopic nature of the vibrational properties in solution, which consists of a combination of the vibrational frequency analyses (VFAs) with two kinds of Hessian matrices, that is, the effective Hessian on the free energy surface (free energy Hessian: "FE-Hessian") and the instantaneous one (instantaneous normal mode Hessian: "INM-Hessian") within QM/MM framework. In these VFAs, the Hessians were obtained by the analytical approach, having the advantages from the aspect of both the computational efficiency and accuracy in comparison to those obtained by the numerical one. In the present study, we have applied them to the glycine aqueous solution.

An improvement in quantum mechanical description of solute-solvent interactions in condensed systems via the number-adaptive multiscale quantum mechanical/molecular mechanical-molecular dynamics method: application to zwitterionic glycine in aqueous solution.

An efficient methodology is presented to improve the QM description of solute-solvent interactions in condensed systems within the quantum mechanical/molecular mechanical (QM/MM) framework. It is based on the recently developed new treatment of the adaptive multiscale QM/MM-MD method, i.e.

Self-association of urea in aqueous solutions: a Voronoi polyhedron analysis study.

Molecular dynamics simulation of the aqueous solutions of urea of seven different concentrations (including neat water as a reference system) has been performed on the isothermal-isobaric (N,p,T) ensemble. The ability of the urea molecules of self-association is investigated by means of the method of Voronoi polyhedra. For this purpose, all the analyses are repeated by removing one of the two components from the sample configurations and considering only the other one.