Assignment of a Physical Energy Scale for the Dimensionless Interaction Energies within the PRIME20 Peptide Model.

We present a calibration scheme to determine the conversion factors from a coarse-grained stochastic approximation Monte Carlo approach using the PRIME20 peptide interaction model to atomistic force-field interaction energies at full explicit aqueous solvation. The conversion from coarse-grained to atomistic structures was performed according to our previously established inverse coarse-graining protocol. We provide a physical energy scale for both the backbone hydrogen bonding interactions and the sidechain interactions by correlating the dimensionless energy descriptors of the PRIME20 model with the energies averaged over molecular dynamics simulations. The conversion factor for these interactions turns out to be around 2 kJ/mol for the backbone interactions, and zero for the sidechain interactions. We discuss these surprisingly small values in terms of their molecular interpretation.

Reverse Mapping of Coarse Grained Polyglutamine Conformations from PRIME20 Sampling.

An inverse coarse-graining protocol is presented for generating and validating atomistic structures of large (bio-) molecules from conformations obtained via a coarse-grained sampling method. Specifically, the protocol is implemented and tested based on the (coarse-grained) PRIME20 protein model (P20/SAMC), and the resulting all-atom conformations are simulated using conventional biomolecular force fields. The phase space sampling at the coarse-grained level is performed with a stochastical approximation Monte Carlo approach. The method is applied to a series of polypeptides, specifically dimers of polyglutamine with varying chain length in aqueous solution. The majority (>70 %) of the conformations obtained from the coarse-grained peptide model can successfully be mapped back to atomistic structures that remain conformationally stable during 10 ns of molecular dynamics simulations. This work can be seen as the first step towards the overarching goal of improving our understanding of protein aggregation phenomena through simulation methods.

Ab Initio Simulation of Raman Fingerprints of Sulfur/Carbon Copolymer Cathodes During Discharge of Li-S Batteries.

Sulfur/carbon copolymers have emerged as promising alternatives for conventional crystalline sulfur cathodes for lithium-sulfur batteries. Among these, sulfur--n--1,3--diisopropenylbenzene (S/DIB) copolymers, which present a 3D network of DIB molecules interconnected via sulfur chains, have particularly shown a good performance and, therefore, have been under intensive experimental and theoretical investigations. However, their structural complexity and flexibility have hindered a clear understanding of their structural evolution during redox reactions at an atomistic level. Here, by performing state-of-the-art ab initio molecular dynamics-based Raman spectroscopy simulations, we investigate the spectral fingerprints of S/DIB copolymers arising from local structures during consecutive reactions with lithium. We discuss Raman spectral changes in particular frequency ranges which are common in S/DIB copolymers having short and those consisting of longer sulfur chains. We also highlight those spectroscopic fingerprints specific to local S/DIB structures containing only short or long sulfur chains. This could help distinguish them experimentally during discharge. Our theoretically predicted results are in a good agreement with experimental Raman measurements on cells at different discharge stages. This work represents an attempt to compute Raman fingerprints of copolymer cathodes during battery operation including quantum-chemical and finite-temperature effects, and provides a guideline for Raman spectral changes of arbitrary electrodes during discharge.

A force field for bio-polymers in ionic liquids (BILFF) - part 2: cellulose in [EMIm][OAc]/water mixtures.

We present the extension of our force field BILFF (Bio-Polymers in Ionic Liquids Force Field) to the bio-polymer cellulose. We already published BILFF parameters for mixtures of ionic liquid 1-ethyl-3-methylimidazolium acetate ([EMIm][OAc]) with water. Our all-atom force field focuses on a quantitative reproduction of the hydrogen bonds in the complex mixture of cellulose, [EMIm]+, [OAc]- and water when compared to reference ab initio molecular dynamics (AIMD) simulations. To enhance the sampling, 50 individual AIMD simulations starting from different initial configurations were performed for cellulose in solvent instead of one long simulation, and the resulting averages were used for force field optimization. All cellulose force field parameters were iteratively adjusted starting from the literature force field of W. Damm et al. We were able to obtain a very good agreement with respect to both the microstructure of the reference AIMD simulations and experimental results such as the system density (even at higher temperatures) and the crystal structure. Our new force field allows performing very long simulations of large systems containing cellulose solvated in (aqueous) [EMIm][OAc] with almost ab initio accuracy.

BILFF: All-Atom Force Field for Modeling Triazolium- and Benzoate-Based Ionic Liquids.

We present an extension of our previously developed all-atom force field BILFF (Bio-polymers in Ionic Liquids Force Field) to three different ionic liquids: 1-ethyl-3-methyl-1,2,3-triazolium acetate ([EMTr][OAc]), 1-ethyl-3-methyl-1,2,3-triazolium benzoate ([EMTr][OBz]), and 1-ethyl-3-methylimidazolium benzoate ([EMIm][OBz]). These ionic liquids are of practical importance as they have the ability to dissolve significant amounts of cellulose even at room temperature. Our force field is optimized to accurately reproduce the strong hydrogen bonding in the system with nearly quantum chemical accuracy. A very good agreement between the microstructure of the quantum chemical simulations over a wide temperature range and experimental density data with the results of BILFF were observed. Non-trivial effects, such as the solvation shell structure and π-π stacking of the cations, are also accurately reproduced. Our force field enables accurate simulations of larger systems, such as solvated cellulose in different (aqueous) ionic liquids, and is the first to present the optimized parameters for mixtures of these solvents and water.

On the Structure of Sulfur/1,3-Diisopropenylbenzene Co-Polymer Cathodes for Li-S Batteries: Insights from Density-Functional Theory Calculations.

Sulfur co-polymers have recently drawn considerable attention as alternative cathode materials for lithium-sulfur batteries, thanks to their flexible atomic structure and the ability to provide high reversible capacity. Here, we report on the atomic structure of sulfur/1,3-diisopropenylbenzene co-polymers (poly(S-co-DIB)) based on the insights obtained from density-functional theory calculations. The focus is set on studying the local structural properties, namely the favorable sulfur chain length (Sn with n = 1 ⋯ 8 ) connecting two DIBs. In order to investigate the effects of the organic groups and sulfur chains separately, we perform series of atomic structure optimizations. We start from simple organic groups connected via sulfur chains and gradually change the structure of the organic groups until we reach a structure in which two DIB molecules are attached via sulfur chains. Additionally, to increase the structural sampling, we perform temperature-assisted minimum-energy structure search on slightly simpler model systems. We find that in DIB-Sn -DIB co-polymers, shorter sulfur chains with n ∼ 4 are preferred, where the stabilization is mostly brought about by the sulfur chains rather than the organic groups. The presented results, corresponding to the fully charged state of the cathode in the thermodynamic limit, have direct applications in the field of lithium-sulfur batteries with sulfur-polymer cathodes.

The important role of non-covalent interactions for the vibrational circular dichroism of lactic acid in aqueous solution.

We present a computational study of vibrational circular dichroism (VCD) in solutions of (S)-lactic acid, relying on ab initio molecular dynamics (AIMD) and full solvation with bulk water. We discuss the effect of the hydrogen bond network on the aggregation behaviour of the acid: while aggregates of the solute represent conditions encountered in a weakly interacting solvent, the presence of water drastically interferes with the clusters - more strongly than originally anticipated. For both scenarios we computed the VCD spectra by means of nuclear velocity perturbation theory (NVPT). The comparison with experimental data allows us to establish a VCD-structure relationship that includes the solvent network around the chiral solute. We suggest that fundamental modes with strong polarisation such as the carbonyl stretching vibration can borrow VCD from the chirally restructured solvent cage, which extends the common explanatory models of VCD generation in aqueous solution.

Switching between Proton Vacancy and Excess Proton Transfer Pathways in the Reaction between 7-Hydroxyquinoline and Formate.

Bifunctional or amphoteric photoacids simultaneously present donor (acidic) and acceptor (basic) properties making them useful tools to analyze proton transfer reactions. In protic solvents, the proton exchange between the acid and the base is controlled by the acidity or basicity strength and typically occurs on two different pathways known as protolysis and hydrolysis. We report here how the addition of a formate base will alter the relative importance of the possible reaction pathways of the bifunctional photoacid 7-hydroxyquinoline (7HQ), which has been recently understood to predominantly involve a hydroxide/methoxide transport mechanism between the basic proton-accepting quinoline nitrogen site toward the proton-donating OH group with a time constant of 360 ps in deuterated methanol (CD3OD). We follow the reaction dynamics by probing the IR-active marker modes of the different charged forms of photoexcited 7HQ, and of formic acid (HCOOD) in CD3OD solution. A comparison of the transient IR spectra as a function of formate concentration, and classical molecular dynamics simulations enables us to identify distinct contributions of "tight" (meaning "contact") and "loose" (i.e., "solvent-separated") 7HQ-formate reaction pairs in our data. Our results suggest that depending on the orientation of the OH group with respect to the quinoline aromatic ring system, the presence of the formate molecule in a proton relay pathway facilitates a net proton transfer from the proton-donating OH group of 7HQ-N* via the methanol/formate bridge toward the quinoline N site.

Effect of anion reorientation on proton mobility in the solid acids family CsHyXO4 (X = S, P, Se, y = 1, 2) from ab initio molecular dynamics simulations.

The high temperature phases of the solid acids CsHSeO4, CsHSO4 and CsH2PO4 show extraordinary high proton conductivities, while the low temperature phases do not conduct protons at all. We systematically investigate proton dynamics in the low and high temperature phases of these compounds by means of ab initio molecular dynamics simulations in order to develop a general picture of the proton transfer mechanism. For all of these compounds, proton conduction follows a Grotthuss mechanism via a combined proton transfer and subsequent structural reorientation of the environment. We demonstrate that the drastically reduced conductivity of the low temperature phases is caused by a highly ordered, rigid hydrogen bond network, while efficient long range proton transfer in the high temperature phases is enabled by the interplay of high proton transfer rates and frequent anion reorientation. Furthermore, we present a simple descriptor for the quantitative prediction of the diffusion coefficient within the solid acids family. As a side result, we show that the rate of the most elementary proton hopping reaction depends on the heavy-atom configuration of the nearest atoms in a ubiquitous manner, and is in turn almost independent from the global nature of the compound, i.e. whether it is organic or inorganic, ordered or disordered.

Optimized effective potentials to increase the accuracy of approximate proton transfer energy calculations in the excited state.

Many fundamental chemical reactions are triggered by electronic excitations. Here, we propose and benchmark a novel approximate first-principles molecular dynamics simulation idea for increasing the computational efficiency of density functional theory-based calculations of the excited states. We focus on obtaining proton transfer energy at the S1 excited state through actual density functional theory calculations at the T1 state with additional optimized effective potentials. The potentials are optimized as such to reproduce the excited-state energy surface obtained using time-dependent density functional theory, but can be generalized to other more accurate quantum chemical methods. We believe that the presented method is not only suitable for studies on excited-state proton transfer and ion mobility in general systems but can also be extended to investigate more involved processes, such as photo-induced isomerization.

Dynamical matrix propagator scheme for large-scale proton dynamics simulations.

We derive a matrix formalism for the simulation of long range proton dynamics for extended systems and timescales. On the basis of an ab initio molecular dynamics simulation, we construct a Markov chain, which allows us to store the entire proton dynamics in an M × M transition matrix (where M is the number of oxygen atoms). In this article, we start from common topology features of the hydrogen bond network of good proton conductors and utilize them as constituent constraints of our dynamic model. We present a thorough mathematical derivation of our approach and verify its uniqueness and correct asymptotic behavior. We propagate the proton distribution by means of transition matrices, which contain kinetic data from both ultra-short (sub-ps) and intermediate (ps) timescales. This concept allows us to keep the most relevant features from the microscopic level while effectively reaching larger time and length scales. We demonstrate the applicability of the transition matrices for the description of proton conduction trends in proton exchange membrane materials.

Exploring non-equilibrium molecular dynamics of mobile protons in the solid acid CsH2PO4 at the micrometer and microsecond scale.

We explicitly compute the non-equilibrium molecular dynamics of protons in the solid acid CsH2PO4 on the micrometer length scale via a multiscale Markov model: The molecular dynamics/matrix propagation (MDM) method. Within the MDM approach, the proton dynamics information of an entire molecular dynamics simulation can be condensed into a single M × M matrix (M is the number of oxygen atoms in the simulated system). Due to this drastic reduction in the complexity, we demonstrate how to increase the length and time scales in order to enable the simulation of inhomogeneities of CsH2PO4 systems at the nanometer scale. We incorporate explicit correlation of protonation dynamics with the protonation state of the neighboring proton sites and illustrate that this modification conserves the Markov character of the MDM method. We show that atomistic features such as the mean square displacement and the diffusion coefficient of the protons can be computed quantitatively from the matrix representation. Furthermore, we demonstrate the application potential of the scheme by computing the explicit dynamics of a non-equilibrium process in an 8 µm CsH2PO4 system during 5 ms.

Carbon Atoms Speaking Out: How the Geometric Sensitivity of 13C Chemical Shifts Leads to Understanding the Colour Tuning of Phycocyanobilin in Cph1 and AnPixJ.

We present a combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics-statistical approach for the interpretation of nuclear magnetic resonance (NMR) chemical shift patterns in phycocyanobilin (PCB). These were originally associated with colour tuning upon photoproduct formation in red/green-absorbing cyanobacteriochrome AnPixJg2 and red/far-red-absorbing phytochrome Cph1Δ2. We pursue an indirect approach without computation of the absorption frequencies since the molecular geometry of cofactor and protein are not accurately known. Instead, we resort to a heuristic determination of the conjugation length in PCB through the experimental NMR chemical shift patterns, supported by quantum chemical calculations. We have found a characteristic correlation pattern of 13C chemical shifts to specific bond orders within the π-conjugated system, which rests on the relative position of carbon atoms with respect to electron-withdrawing groups and the polarisation of covalent bonds. We propose the inversion of this regioselective relationship using multivariate statistics and to apply it to the known experimental NMR chemical shifts in order to predict changes in the bond alternation pattern. Therefrom the extent of electronic conjugation, and eventually the change in absorption frequency, can be derived. In the process, the consultation of explicit mesomeric formulae plays an important role to qualitatively account for possible conjugation scenarios of the chromophore. While we are able to consistently associate the NMR chemical shifts with hypsochromic and bathochromic shifts in the Pg and Pfr, our approach represents an alternative method to increase the explanatory power of NMR spectroscopic data in proteins.

ab-Initio Study of Hydrogen Bond Networks in 1,2,3-Triazole Phases.

The research in storage and conversion of energy is an everlasting process. The use of fuel cells is very tempting but up to now there are still several conceptual challenges to overcome. Especially, the requirement of liquid water causes difficulties due to the temperature limit. Therefore, imidazoles and triazoles are increasingly investigated in a manifold of experimental and theoretical publications as they are both very promising in overcoming this problem. Recently, triazoles were found to be superior to imidazoles in proton conduction. An ab-initio molecular dynamics simulation of pure triazole phases for investigating the behavior of both tautomer species of the triazole molecule has never been done. In this work, we investigate the structural and dynamical properties of two different solid phases and the liquid phase at two different temperatures. We are able to show how the distinct tautomers contribute to the mechanism of proton conduction, to compute dynamical properties of the four systems and to suggest a mechanism of reorientation in solid phase.

Dissolving Cellulose in 1,2,3-Triazolium- and Imidazolium-Based Ionic Liquids with Aromatic Anions.

We present 1,2,3-triazolium- and imidazolium-based ionic liquids (ILs) with aromatic anions as a new class of cellulose solvents. The two anions in our study, benzoate and salicylate, possess a lower basicity when compared to acetate and therefore should lead to a lower amount of N-heterocyclic carbenes (NHCs) in the ILs. We characterize their physicochemical properties and find that all of them are liquids at room temperature. By applying force field molecular dynamics (MD) simulations, we investigate the structure and dynamics of the liquids and find strong and long-lived hydrogen bonds, as well as significant π-π stacking between the aromatic anion and cation. Our ILs dissolve up to 8.5 wt.-% cellulose. Via NMR spectroscopy of the solution, we rule out chain degradation or derivatization, even after several weeks at elevated temperature. Based on our MD simulations, we estimate the enthalpy of solvation and derive a simple model for semi-quantitative prediction of cellulose solubility in ILs. With the help of Sankey diagrams, we illustrate the hydrogen bond network topology of the solutions, which is characterized by competing hydrogen bond donors and acceptors. The hydrogen bonds between cellulose and the anions possess average lifetimes in the nanosecond range, which is longer than found in common pure ILs.

Ultrafast Proton Transport between a Hydroxy Acid and a Nitrogen Base along Solvent Bridges Governed by the Hydroxide/Methoxide Transfer Mechanism.

Aqueous proton transport plays a key role in acid-base neutralization and energy transport through biological membranes and hydrogen fuel cells. Extensive experimental and theoretical studies have resulted in a highly detailed elucidation of one of the underlying microscopic mechanisms for aqueous excess proton transport, known as the von Grotthuss mechanism, involving different hydrated proton configurations with associated high fluxional structural dynamics. Hydroxide transport, with approximately 2-fold-lower bulk diffusion rates compared to those of excess protons, has received much less attention. We present femtosecond UV/IR pump-probe experiments and ab initio molecular dynamics simulations of different proton transport pathways of bifunctional photoacid 7-hydroxyquinoline (7HQ) in water/methanol mixtures. For 7HQ solvent-dependent photoacidity, free-energy-reactivity correlation behavior and quantum mechanics/molecular mechanics (QM/MM) trajectories point to a dominant OH-/CH3O- transport pathway for all water/methanol mixing ratios investigated. Our joint ultrafast infrared spectroscopic and ab initio molecular dynamics study provides conclusive evidence for the hydrolysis/methanolysis acid-base neutralization pathway, as formulated by Manfred Eigen half a century ago. Our findings on the distinctly different acid-base reactivities for aromatic hydroxyl and aromatic nitrogen functionalities suggest the usefulness of further exploration of these free-energy-reactivity correlations as a function of solvent polarity. Ultimately the determination of solvent-dependent acidities will contribute to a better understanding of proton-transport mechanisms at weakly polar surfaces and near polar or ionic regions in transmembrane proton pump proteins or hydrogen fuel cell materials.

Efficient representation of the linear density-density response function.

We present a thorough derivation of the mathematical foundations of the representation of the molecular linear electronic density-density response function in terms of a computationally highly efficient moment expansion. Our new representation avoids the necessities of computing and storing numerous eigenfunctions of the response kernel by means of a considerable dimensionality reduction about from 103 to 101 . As the scheme is applicable to any compact, self-adjoint, and positive definite linear operator, we present a general formulation, which can be transferred to other applications with little effort. We also present an explicit application, which illustrates the actual procedure for applying the moment expansion of the linear density-density response function to a water molecule that is subject to a varying external perturbation potential. © 2019 The Authors. Journal of Computational Chemistry published by Wiley Periodicals, Inc.

The Conformational Ensemble of Polyglutamine-14 Chains: Specific Influences of Solubility Tail and Chromophores.

We address polyglutamine-14 in aqueous solution with specific chromophores and a solubility chain by means of a multiscale simulation approach, combining atomistic molecular dynamics simulations and coarse-grained Monte-Carlo conformational sampling. Despite the intrinsically disordered nature of the amyloidogenic polyglutamine, we observe transient characteristic structural motifs which exhibit a specific hydrogen bonding pattern. We illustrate the relationship between structure pattern and the distance distribution of a pair of chromophores attached to the peptide termini, in light of specific influence of a short solubility tail and the chromophores themselves on the conformational ensemble.

Effect of puckering motion and hydrogen bond formation on the vibrational circular dichroism spectrum of a flexible molecule: the case of (S)-1-indanol.

The influence of flexibility and hydrogen bond formation on the IR absorption and vibrational circular dichroism (VCD) spectrum of a floppy protic molecule, namely, (S)-1-indanol, is studied in both non-polar CCl4 and polar DMSO solvents. The experimental IR absorption and VCD spectra obtained by Fourier transform spectroscopy are interpreted using both static density functional theory (DFT) calculations and first principles molecular dynamics (FPMD) within DFT, using the nuclear velocity perturbation theory (NVPT). Simulation of the spectra based on static optimised geometries is not sufficient in CCl4 and going beyond static calculations is mandatory for satisfactorily reproducing the VCD spectra. The FPMD results obtained in DMSO indicate that (S)-1-indanol is hydrogen-bonded to one DMSO molecule. As a result, static "cluster-in-the-bulk" DFT calculations in which the solute-solvent interaction is modeled as the most stable (S)-1-indanol:DMSO complexes in a DMSO continuum yield satisfactory agreement with the experiment. Correspondence between experimental and simulated spectra is slightly improved when the VCD spectrum is calculated as the summed contributions of snapshots extracted from FPMD trajectories, due to better sampling of the potential-energy surface. Finally, NVPT calculations further improve the description of experimental spectra by taking into account higher-energy structures, which are not necessary local minima.

Simulating structure and dynamics in small droplets of 1-ethyl-3-methylimidazolium acetate.

To investigate the structure and dynamics of small ionic liquid droplets in gas phase, we performed a DFT-based ab initio molecular dynamics study of several 1-ethyl-3-methylimidazolium acetate clusters in vacuum as well as a bulk phase simulation. We introduce an unbiased criterion for average droplet diameter and density. By extrapolation of the droplet densities, we predict the experimental bulk phase density with a deviation of only a few percent. The hydrogen bond geometry between cations and anions is very similar in droplets and bulk, but the hydrogen bond dynamics is significantly slower in the droplets, becoming slower with increasing system size, with hydrogen bond lifetimes up to 2000 ps. From a normal mode analysis of the trajectories, we identify the modes of the ring proton C-H stretching, which are strongly affected by hydrogen bonding. From analyzing these, we find that the hydrogen bond becomes weaker with increasing system size. The cations possess an increased concentration inside the clusters, whereas the anions show an excess concentration on the outside. Almost all anions point towards the droplet center with their carboxylic groups. Ring stacking is found to be a very important structural motif in the droplets (as in the bulk), but side chain interactions are only of minor importance. By using Voronoi tessellation, we define the exposed droplet surface and find that it consists mainly of hydrogen atoms from the cation's and anion's methyl and ethyl groups. Polar atoms are rarely found on the surface, such that the droplets appear completely hydrophobic on the outside.