H-bond Lifetimes Research Articles

Nonlinear composition dependence of hydrogen bond lifetime in water-DMSO binary mixtures: The role of hydrophobic interaction.

The lifetime of a hydrogen bond between water and dimethyl sulfoxide (DMSO) is found to be considerably longer than that between two water molecules in neat water. This is counter-intuitive because the charge on the oxygen in DMSO is considerably less than that in water. Additionally, the strength of the water-dimethyl sulfoxide (w-D) hydrogen bond is found to be strongly composition dependent; the lifetime of the hydrogen bond is ten times larger at 30% than at very low concentrations. Using computer simulations, we perform microscopic structural and dynamic analysis to find that these anomalies arise at least partly from an "action-at-a-distance" effect where the attraction between the hydrophobic methyl groups results in the self-aggregation of DMSO molecules that "cages" both the rotational and linear motions of the molecules involved. This is reflected in the observed strong correlation of the lifetime with the local coordination number of the associated methyl groups. The elongated w-D h-bond lifetime causes a slowdown of collective dynamics and affects the lifetime of the w-w h-bond. This nonlinear feedback mechanism explains the strong composition dependence of viscosity and is anticipated to play a dominant role in many self-assemblies. Furthermore, the w-D hydrogen bond breaking mechanism changes from low to high DMSO concentration, a phenomenon not anticipated a priori. We introduce a new order parameter-based free energy surface of the bond breaking pathway. A two-dimensional transition state rate theory calculation is performed for the lifetime of the w-D h-bond that is found to be semi-quantitatively accurate.

Influence of cholesterol on hydrogen-bond dynamics of water molecules in lipid-bilayer systems at varying temperatures.

Cholesterol (Chol) plays a crucial role in shaping the intricate physicochemical attributes of biomembranes, exerting a considerable influence on water molecules proximal to the membrane interface. In this study, we conducted molecular dynamics simulations on the bilayers of two lipid species, dipalmitoylphosphatidylcholine (DPPC) and palmitoyl sphingomyelin; they are distinct with respect to the structures of the hydrogen-bond (H-bond) acceptors. Our investigation focuses on the dynamic properties and H-bonds of water molecules in the lipid-membrane systems, with a particular emphasis on the influence of Chol at varying temperatures. Notably, in the gel phase at 303K, the presence of Chol extends the lifetimes of H-bonds of the oxygen atoms acting as H-bond acceptors within DPPC with water molecules by a factor of 1.5-2.5. In the liquid-crystalline phase at 323K, on the other hand, H-bonding dynamics with lipid membranes remain largely unaffected by Chol. This observed shift in H-bonding states serves as a crucial key to unraveling the subtle control mechanisms governing water dynamics in lipid-membrane systems.

Nonequilibrium Ab Initio Molecular Dynamics Simulation of Water Splitting at Fe2O3-Hematite/Water Interfaces in an External Electric Field.

In the exploration of the optimal material for achieving the photoelectrochemical dissociation of water into hydrogen, hematite (α-Fe2O3) emerges as a highly promising candidate for proof-of-concept demonstrations. Recent studies suggest that the concurrent application of external electric fields could enhance the photoelectrochemical (PEC) process. To delve into this, we conducted nonequilibrium ab initio molecular dynamics (NE-AIMD) simulations in this study, focusing on hematite-water interfaces at room temperature under progressively stronger electric fields. Our findings reveal intriguing evidence of water molecule adsorption and dissociation, as evidenced by an analysis of the structural properties of the hydrated layered surface of the hematite-water interface. Additionally, we scrutinized intermolecular structures using radial distribution functions (RDFs) to explore the interaction between the hematite slab and water. Notably, the presence of a Grotthuss hopping mechanism became apparent as the electric field strength increased. A comprehensive discussion based on intramolecular geometry highlighted aspects such as hydrogen-bond lengths, H-bond angles, average H-bond numbers, and the observed correlation existing among the hydrogen-bond strength, bond-dissociation energy, and H-bond lifetime. Furthermore, we assessed the impact of electric fields on the librational, bending, and stretching modes of hydrogen atoms in water by calculating the vibrational density of states (VDOS). This analysis revealed distinct field effects for the three characteristic band modes, both in the bulk region and at the hematite-water interface. We also evaluated the charge density of active elements at the aqueous hematite surface, delving into field-induced electronic charge-density variations through the Hirshfeld charge density analysis of atomic elements. Throughout this work, we drew clear distinctions between parallel and antiparallel field alignments at the hematite-water interface, aiming to elucidate crucial differences in local behavior for each surface direction of the hematite-water interface.

Effect of electronegative atoms on [formula omitted] – [formula omitted] stacking and hydrogen bonding behavior in simple aromatic molecules — An Ab initio MD study

Ab initio molecular dynamics studies have been performed on fluorobenzene, phenol, and aniline, which have the three most electronegative atoms, fluorine, oxygen, and nitrogen, respectively. Radial distribution functions show strong hydrogen bonding in the phenolic –OH group, whereas it is less prominent in the –NH2 group of aniline. Fluorobenzene does not show strong hydrogen bonds as no solvation shell is found between the fluorine atom and different aromatic hydrogens of the molecule. Spatial distribution functions show that the nitrogen atom of aniline interacts with the aromatic plane, the oxygen atom of phenol is concentrated near the –OH group and fluorobenzene’s fluorine atom interacts with the para hydrogen. Liquid phase dimer structures of these systems reveal that perpendicular orientation (Y-shaped) is preferred over parallel ones. Almost half of the total dimer population tends to prefer 90∘±30° angle. H-bond analyses show that fluorobenzene has the longest mean H-bond lifetime for the H-bond between the aromatic hydrogens and the fluorine atoms, whereas the aniline has the least. The mean lifetime between aromatic hydrogens and electronegative atoms increases steadily from aniline to fluorobenzene. Phenolic –OH and amino –NH2 groups show considerably longer mean H-bond lifetime than the aromatic hydrogens. Gas-phase binding energies obtained from quantum chemical calculations show that aniline and phenol dimers have higher binding energy values than the fluorobenzene dimer. Only the phenol dimer shows a perpendicular structure as a stable one, while aniline and fluorobenzene prefer the parallel orientation.

TMAO: Protecting proteins from feeling the heat

Osmolytes are ubiquitous in the cell and play an important role in controlling protein stability under stress. The natural osmolyte trimethylamine N-oxide (TMAO) is used by marine animals to counteract the effect of pressure denaturation at large depths. The molecular mechanism of TMAO stabilization against pressure and urea denaturation has been extensively studied, but unlike the case of other osmolytes, the ability of TMAO to protect proteins from high temperature has not been quantified. To reveal the effect of TMAO on folded and unfolded protein ensembles and the hydration shell at different temperatures, we study a mutant of the well-characterized, fast-folding model protein B (PRB). We carried out, in total, >190 μs all-atom simulations of thermal folding/unfolding of PRB at multiple temperatures and concentrations of TMAO. The simulations show increased thermal stability of PRB in the presence of TMAO. Partly structured, compact ensembles are favored over the unfolded state. TMAO forms two shells near the protein: an outer shell away from the protein surface has altered H-bond lifetimes of water molecules and increases hydration of the protein to help stabilize it; a less-populated inner shell with an opposite TMAO orientation closer to the protein surface binds exclusively to basic side chains. The cooperative cosolute effect of the inner and outer shell TMAO has a small number of TMAO molecules “herding” water molecules into two hydration shells at or near the protein surface. The stabilizing effect of TMAO on our protein saturates at 1 M despite higher TMAO solubility, so there may be little evolutionary pressure for extremophiles to produce higher intracellular TMAO concentrations, if true in general.

Surface Properties of N,N-Dimethylformamide-Water Mixtures, As Seen from Computer Simulations.

The liquid-vapor interface of N,N-dimethylformamide (DMF)-water mixtures, spanning the entire composition range, is investigated in detail at 298 K by molecular dynamics simulation and intrinsic surface analysis. DMF molecules are found to adsorb strongly at the liquid surface, but this adsorption extends only to the first molecular layer. Water and DMF molecules mix with each other on the molecular scale even in the surface layer; thus, no marked self-association of any of the components is seen at the liquid surface. The major surface component prefers such orientation in which the molecular dipole vector lays parallel with the macroscopic plane of the surface. On the other hand, the preferred orientation of the minor component is determined, at both ends of the composition range, by the possibility of H-bond formation with the major component. The lack of H-donating ability of DMF leads to a rapid breakup of the percolating H-bond network at the surface; due to the strong adsorption of DMF, this breakup occurs below the bulk phase DMF mole fraction of 0.03. The disruption of the surface H-bond network also accelerates the exchange of both species between the liquid surface and bulk liquid phase, although, for water, this effect becomes apparent only above a bulk phase DMF mole fraction of 0.4. H-bonds formed by a DMF and a water molecule live, on average, 25-60% longer than those formed by two water molecules at the liquid surface. A similar, but smaller (i.e., about 10-20%) difference is seen in the bulk liquid phase. The enhanced surface mobility of the molecules results in 2-6 times larger diffusion coefficient and 2-5 times shorter H-bond lifetime values at the liquid surface than in the bulk liquid phase. The diffusion of both molecules is slowed down in the presence of the other species; in the case of DMF, this effect is caused by the formation of water-DMF H-bonds, whereas for water, steric hindrances imposed by the bulky DMF neighbors are responsible for this slowing down.

Insight into the mechanism of DNA synthesis by human terminal deoxynucleotidyltransferase.

Terminal deoxynucleotidyltransferase (TdT) is a member of the DNA polymerase X family that is responsible for random addition of nucleotides to single-stranded DNA. We present investigation into the role of metal ions and specific interactions of dNTP with active-site amino acid residues in the mechanisms underlying the recognition of nucleoside triphosphates by human TdT under pre-steady-state conditions. In the elongation mode, the ratios of translocation and dissociation rate constants, as well as the catalytic rate constant were dependent on the nature of the nucleobase. Preferences of TdT in dNTP incorporation were researched by molecular dynamics simulations of complexes of TdT with a primer and dNTP or with the elongated primer. Purine nucleotides lost the "summarised" H-bonding network after the attachment of the nucleotide to the primer, whereas pyrimidine nucleotides increased the number and relative lifetime of H-bonds in the post-catalytic complex. The effect of divalent metal ions on the primer elongation revealed that Me<sup>2+</sup> cofactor can significantly change parameters of the primer elongation by strongly affecting the rate of nucleotide attachment and the polymerisation mode.

Transition pathway of hydrogen bond switching in supercooled water analyzed by the Markov state model.

In this work, we examine hydrogen-bond (H-bond) switching by employing the Markov State Model (MSM). During the H-bond switching, a water hydrogen initially H-bonded with water oxygen becomes H-bonded to a different water oxygen. MSM analysis was applied to trajectories generated from molecular dynamics simulations of the TIP4P/2005 model from a room-temperature state to a supercooled state. We defined four basis states to characterize the configuration between two water molecules: H-bonded ("H"), unbound ("U"), weakly H-bonded ("w"), and alternative H-bonded ("a") states. A 16 × 16 MSM matrix was constructed, describing the transition probability between states composed of three water molecules. The mean first-passage time of the H-bond switching was estimated by calculating the total flux from the HU to UH states. It is demonstrated that the temperature dependence of the mean first-passage time is in accordance with that of the H-bond lifetime determined from the H-bond correlation function. Furthermore, the flux for the H-bond switching is decomposed into individual pathways that are characterized by different forms of H-bond configurations of trimers. The dominant pathway of the H-bond switching is found to be a direct one without passing through such intermediate states as "w" and "a," the existence of which becomes evident in supercooled water. The pathway through "w" indicates a large reorientation of the donor molecule. In contrast, the pathway through "a" utilizes the tetrahedral H-bond network, which is revealed by the further decomposition based on the H-bond number of the acceptor molecule.

Supercritical Water is not Hydrogen Bonded.

Thinking about water is inextricably linked to hydrogen bonds, which are highly directional in character and determine the unique structure of water, in particular its tetrahedral H‐bond network. Here, we assess if this common connotation also holds for supercritical water. We employ extensive ab initio molecular dynamics simulations to systematically monitor the evolution of the H‐bond network mode of water from room temperature, where it is the hallmark of its fluctuating three‐dimensional network structure, to supercritical conditions. Our simulations reveal that the oscillation period required for H‐bond vibrations to occur exceeds the lifetime of H‐bonds in supercritical water by far. Instead, the corresponding low‐frequency intermolecular vibrations of water pairs as seen in supercritical water are found to be well represented by isotropic van‐der‐Waals interactions only. Based on these findings, we conclude that water in its supercritical phase is not a H‐bonded fluid.

Quantum chemical and molecular dynamics modeling of interaction of isomolecular dipeptides of α-l-alanyl-α-l-alanine and β-alanyl-β-alanine with sodium dodecyl sulfate micelles

Quantum chemical investigation of α-l-alanyl-α-l-alanine and β-alanyl-β-alanine complexes with SDS dimer as an anion micelle fragment in polarizable continuum has been carried out by using of DFT method with B97-D/6-311++G(3d,3p) level. The variation of peptide structure and the difference in energies of free peptides, SDS dimer and their complexes have been analyzed. Optimized configurations of complexes are stabilized by hydrogen bonds of (H2)NH…O(S) type. The localization of α-l-alanyl-α-l-alanine among the charged groups of SDS dimer is more preferable. The localization of β-alanyl-β-alanine among the charged groups or in the dimer hydrophpbic canal results in close values of the complex formation energy. More favorite change of energy and shorter length of hydrogen bond of (H2)NH…O(S) type have been revealed for complex formation between SDS dimer and β-alanyl-β-alanine as opposed to α-l-alanyl-α-l-alanine. Molecular dynamics simulation of adsorption of the peptides on SDS micelle has been performed in NPT ensemble at 0.1 MPa and 298 K. The cell under study contained 14,678 water molecules, one peptide zwitter-ion, and the micelle including 64 SDS monomers. Most probable localization of peptide atoms relative the micelle has been analyzed. The peptide – SDS micelle interaction is accompanied by diminish of average number of peptide – water H-bonds and the formation of at the mean two H-bonds with SDS. Some peculiarities of adsorption of the isomolecular peptides on SDS micelle are appeared in different values of H-bond lifetimes, different probability of formation of H-bond of NH3+…−O3SO or NH3+…O(SO3−) types, and localization of peptide zwitter-ions outside or within double electrical layer of the micelle.

Aqueous solvation of the chloride ion revisited with density functional theory: impact of correlation and exchange approximations.

The specificity of aqueous halide solvation is fundamental to a wide range of bulk and interfacial phenomena spanning from biology to materials science. Halide polarizability is thought to drive the ion specificity, and if so, it is essential to have an accurate description of the electronic properties of halide ions in water. To this end, the solvation of the chloride anion, Cl- has been reinvestigated with state-of-the-art density functional theory. Specifically, the PBE-D3, PBE0-D3, and SCAN functionals have been employed to probe the impact of correlation and exchange approximations. Anticipating the findings, adding exact exchange improves the electronic structure, but simultaneously significantly reduces the Cl- polarizability, resulting in an over-structured Cl-O radial distribution function (RDF) and longer water H-bond lifetimes to Cl-. SCAN does not yield as much improvement in the energetics of Cl- relative to bulk water, but does result in a smaller reduction of the polarizability and thus a less structured Cl-O RDF, which agrees better with experiment. Special consideration is therefore warranted in assessing the impact of exchange on the energy, charge density, and the charge density response when designing and testing hybrid functionals for aqueous halide solvation.

Consistency of geometrical definitions of hydrogen bonds based on the two-dimensional potential of mean force with respect to the time correlation in liquid water over a wide range of temperatures

We examine the temperature dependence of the hydrogen-bond (H-bond) dynamics in supercooled water through the molecular dynamics (MD) simulations using the TIP4P/2005 model. First, we investigate the two-dimensional (2D) potential of mean force (PMF) for the H-bond definition using a pair of distance and angle coordinates between two water molecules. Specifically, we utilize four combinations of the geometrical variables, R-β, r-α, r-γ, and r-ψ, where R and r are the intermolecular O-O and O-H distances, respectively. β and α represent the angles of O-OH and O-HO, respectively, while ψ and γ are angles introduced in terms of the intermolecular O-H vector and the HOH plane of the H-bond acceptor. The consistency among the four definitions of H-bond was then examined by identifying the saddle point on the 2D PMF and analyzing the time correlation function of H-bond. It was found over a wide range of temperatures from the ambient to supercooled that the H-bond definition does not affect the long-time H-bond correlation function and correspondingly, the H-bond lifetime τHB.

Effect of Na and Cl ions on water evaporation on graphene oxide

Using molecular dynamics simulations, we investigate the influence of Na and Cl ions on the evaporation of nanoscale water on graphene oxide surfaces. As the concentration of NaCl increases from 0 to 1.5 M, the evaporation rate shows a higher decrease on patterned graphene oxide than that on homogeneous graphene oxide. The analysis shows an obvious decrease in the evaporation rate from unoxidized regions, which can be attributed to the increased amount of Na+ ions near the contact lines. The proximity of Na+ significantly extends the H-bond lifetime of the outermost water molecules, which reduces the number of water molecules diffusing from the oxidized to unoxidized regions. Moreover, the effect of the ions on water evaporation is less significant when the oxidation degree varies in a certain range. Our findings advance the understanding of the evaporation process in the presence of ions and highlight the potential application of graphene oxide in achieving controllable evaporation of liquids.

Water-mediated weakening of inter-ionic interactions in aqueous mixtures of ionic liquid: An investigation combining quantum chemical calculations and molecular dynamics simulations

Quantum chemical calculations and molecular dynamic simulations have been performed to understand the structure and energetics of ionic liquid (IL) in presence of water. Addition of water is found to induce charge flow from the anion to cation, reducing the strength of the electrostatic interactions between the ion-pair without changing the interionic distance. Composition dependent isotropic (α0) and anisotropic (αaniso) components of the total polarizability do not show any dependence on the number of water molecules present in the (IL + water) binary mixture. Vibrational density of states for ions obtained from simulated velocity auto correlation function do not show any composition dependence. These provide much-needed explanation for the insensitivity of spectral shift to water concentration reported in OHD-RIKES measurements with IL + water mixtures. Continuous and structural H-bond lifetimes predict a decrease of both with water concentration. This can be understood in terms of concomitant reductions in inter-ionic electrostatic interactions and solution viscosity.

High temperature aqueous solvent effect on translational and hydrogen bond dynamics of the hydroxyl radical — MD simulation study

MD simulations using flexible models were performed to show how velocity autocorrelation functions, diffusion (DOH) and self-diffusion (Dw) coefficients, continuous and intermittent lifetimes of H-donor and H-acceptor bonds depend on: i) transformations in the hydrogen-bond network (HBN) of water below the critical point, and ii) decreasing density at the supercritical isotherm (∼670 K). Contrary to simulations neglecting short-range hydrogen-oxygen interactions, we show that complexation of OHaq with H2O is enhanced by breakage of the continuous HBN, resulting in the increase of OHaq hydrodynamic radius and the DOH values smaller than Dw by 30%. Difference between DOH and Dw increases to 65% at 670 K below the critical density. It is explained by enhanced aggregation of water molecules around OHaq, earlier recognized as the self-trapping mechanism. Except near-ambient conditions, the intermittent lifetime of H-bonds is longer than the translational time, indicating that OHaq is complexed with water and moves as a molecular aggregate.

How do hydrogen bonds break in supercooled water?: Detecting pathways not going through saddle point of two-dimensional potential of mean force.

Supercooled water exhibits remarkably slow dynamics similar to the behavior observed for various glass-forming liquids. The local order of tetrahedral structures due to hydrogen-bonds (H-bonds) increases with decreasing temperature. Thus, it is important to clarify the temperature dependence of the H-bond breakage process. This was investigated here using molecular dynamics simulations of TIP4P supercooled water. The two-dimensional (2D) potential of mean force (PMF) is presented using combinations of intermolecular distance and angle between two water molecules. The saddle point of the 2D PMF suggests the presence of the transition state that distinguishes between H-bond and non H-bond states. However, we observed pathways not going through this saddle point particularly at supercooled states, which are due to translational rather than rotational motions of the molecules. We quantified the characteristic time scales of rotational and translational H-bond breakages. The time scale of the translational H-bond breakage shows a non-Arrhenius temperature dependence comparable to that of the H-bond lifetime. This time scale is relevant for the temperature dependence of the transmission coefficient based on the transition state theory. The translational H-bond breakage is also related to cage-jumps observed in glass-forming liquids, which mostly involve spatially correlated molecules. Our findings warrant further exploration of an appropriate free-energy surface or reaction coordinates beyond the geometrical variables of the water dimer to describe a possible saddle point related to collective jump motions.

Orientational dynamics in a room temperature ionic liquid: Are angular jumps predominant?

Reorientational dynamics of the constituent ions in a room temperature ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]), are explored via molecular dynamics simulations, and several features of orientation dynamics are summarized. The anion, [PF6]-, not only exhibits a higher propensity to orientation jumps than the cation, [BMIM]+ but also accesses a wider jump angle distribution and larger peak-angle. Jump and waiting time distributions for both the ions depict power-law dependences, suggesting temporally heterogeneous dynamics for the medium. This heterogeneity feature is further highlighted by the finding that the simulated first rank (ℓ = 1) and second rank (ℓ = 2) average reorientational correlation times reflect a severe break-down of Debye's ℓ(ℓ + 1) law for orientational diffusion in an isotropic homogeneous medium. Simulated average H-bond lifetime resides between the mean orientation jump and waiting times, while the structural H-bond relaxation suggests, as in normal liquids, a pronounced presence of translational motion of the partnering ions. Average simulated jump trajectories reveal a strong rotation-translation coupling and indicate relatively larger changes in spatial and angular arrangements for the anion during an orientation jump. In fact, a closer inspection of all these results points toward more heterogeneous dynamics for [PF6]- than [BMIM]+. This is a new observation and may simply be linked to the ion-size. However, such a generalization warrants further study.

Molecular dynamics studies show solvation structure of type III antifreeze protein is disrupted at low pH

Antifreeze proteins are a class of biological molecules of interest in many research and industrial applications due to their highly specialized function, but there is little information of their stability and properties under varied pH derived from computational studies. To gain novel insights in this area, we conducted molecular dynamics (MD) simulations with the antifreeze protein 1KDF at varied temperatures and pH. Water solvation and H-bond formation around specific residues – ASN14, THR18 and GLN44 – involved in its antifreeze activity were extensively studied. We found that at pH1 there was a disruption in water solvation around the basal and the ice binding surfaces of the molecule. This was induced by a small change in the secondary structure propensities of some titrable residues, particularly GLU35. This change explains the experimentally observed reduction in antifreeze activity previously reported for this protein at pH1. We also found that THR18 showed extremely low H-bond formation, and that the three antifreeze residues all had very low average H-bond lifetimes. Our results confirm long-standing assumptions that these small, compact molecules can maintain their antifreeze activity in a wide range of pH, while demonstrating the mechanism that may reduce antifreeze activity at low pH. This aspect is useful when considering industrial and commercial use of antifreeze proteins subject to extreme pH environments, in particular in food industrial applications.

Structural aspects of the topological model of the hydrogen bond in water on auto-dissociation via proton transfer.

Molecular dynamics (MD) simulations were used to investigate the structure and lifetimes of hydrogen bonds and auto dissociation via proton transfer in bulk water using a reactive and dissociative all-atom potential that has previously been shown to match a variety of water properties and proton transfer. Using the topological model, each molecule's donated and accepted hydrogen bonds were labeled relative to the other hydrogen bonds on neighboring waters, providing a description of the effect of these details on the structure, dynamics and autoionization of water molecules. In agreement with prior data, asymmetric bonding at the sub-100 femtosecond timescale is observed, as well as the existence of linear, bifurcated, and dangling hydrogen bonds. The lifetime of the H-bond, 2.1 ps, is consistent with experimental data, with short time librations on the order of femtoseconds. The angular correlation functions, the presence of a second shell water entering the first shell, and OH vibrational stretch frequencies were all consistent with experiment or ab initio calculations. The simulations show short-lived (femtoseconds) dissociation of a small fraction of water molecules followed by rapid recombination. The role of the other H-bonds to the acceptor and on the donor plays an important part in proton transfer between the molecules in auto dissociation and is consistent with the role of a strong electric field caused by local (first and second shell) waters on initiating dissociation. The number of H-bonds to the donor water is 4.3 per molecule in the simulations, consistent with previous data regarding the number of hydrogen bonds required to generate this strong local electric field that enhances dissociation. The continuous lifetime autocorrelation function of the H-bond for those molecules that experience dissociation is considerably longer than that for all molecules that show no proton transfer.

Water Dynamics and Proton-Transport Mechanisms of Nafion 117/Phosphotungstic Acid Composite Membrane: A Molecular Dynamics Study.

The use of a Nafion/phosphotungstic acid composite membrane and the impact of varying concentration of heteropoly acid (HPA) on the well-known effective mechanisms of proton transport were investigated by using classical and quantum hopping molecular dynamics simulation. Our simulations demonstrated that the HPA particles have a favorable influence on the Grotthuss mechanism in proton transportation at low hydration levels. From radial distribution function examinations, it was found that HPA particles were solvated with water and also exhibited stronger affinity toward hydronium ions. It can be concluded that addition of hydrophilic particles such as HPA improved proton conductivity. To assess this effectiveness, lifetime and half-life of the hydrogen bond (H-bond) network in the formed water clusters were investigated at different HPA concentrations. The analysis of H-bond network stability revealed that the lifetime of H-bonds between water molecules and protons decreased with increasing HPA concentration. Moreover, we found that the H-bond network between water molecules was more stable, and the mismatch between simulated bulk water and those formed water clusters in the considered systems decreased upon HPA addition. Indeed, for HPA doped membrane, the activation energy of proton transfer process from a hydronium ion to a water molecule was lower than for the undoped system. The water diffusion coefficient decreased and that of the hydronium ion enhanced with an increase in HPA doping level.