arXiv subjects

Pavel Jungwirth

Publications and source records attributed to Pavel Jungwirth.

12 recordsLinked to original sources

arXiv2026

Uncertainty Quantification for Free Energy Calculations by Generalized Hierarchical Bayesian Inference

Free energy calculations are routinely used to study molecular processes inaccessible to unbiased molecular dynamics, but their utility ultimately depends on knowing when and how much their predictions can be trusted. Uncertainty estimation is therefore essential for distinguishing genuine physical features of a free energy profile from artifacts arising from limited simulation data or inadequate sampling. Gaussian processes have emerged as a powerful framework for reconstructing free energy profiles together with predictive uncertainties. However, existing implementations typically condition on fixed hyperparameters and observation noise, preventing predictive uncertainties from adapting to the information content of the simulation data. Here, we develop a generalized hierarchical Gaussian process framework that accounts for these neglected sources of uncertainty. Applications to umbrella sampling and extended Lagrangian metadynamics of peptide-lipid membrane interactions demonstrate that the resulting uncertainty estimates track reconstruction errors across a wide range of sampling and data conditions.

physics.chem-ph↗

arXiv2026

How Alkali Metal Cations Affect the Structure and Reactivity of the Hydrated Dielectron

Hydrated electrons of opposite spins pair to form dielectrons at sufficiently high concentrations that can be achieved by dissolution of alkali metals in water. While experimental investigations of these systems are challenging due to their vigorous, even explosive, reactivity, simulations open the possibility to characterize the structure and reactivity of hydrated dielectrons and the effects of alkali cations thereon. Here, we present ab initio molecular dynamics simulations of a hydrated dielectron without or with explicit Li$^+$ or Cs$^+$ counterions. While the overall solvation structure is preserved in all these systems, the presence of cations has a distinct effect of increasing the dielectron gyration radius by about 10% and forming cation-specific cation-dielectron arrangements. Moreover, analysis of water bond lengths reveals in all studied systems a substantial elongation of first-shell O-H bonds oriented toward the dielectron, providing a structural explanation for vibrational red-shifts observed in resonance Raman measurements. Finally, at the 10 ps simulation timescale, rare reactive events were observed, albeit only for the system without metal cations, where hydride intermediates stable on picosecond timescales were identified. These observations also suggest that on the investigated timescales, metal cations may suppress hydrated dielectron reactivity.

physics.chem-ph↗

arXiv2025

Bayesian learning for accurate and robust biomolecular force fields

Molecular dynamics is a valuable tool to probe biological processes at the atomistic level - a resolution often elusive to experiments. However, the credibility of molecular models is limited by the accuracy of the underlying force field, which is often parametrized relying on ad hoc assumptions. To address this gap, we present a Bayesian framework for learning physically grounded parameters directly from ab initio molecular dynamics data. By representing both model parameters and data probabilistically, the framework yields interpretable, statistically rigorous models in which uncertainty and transferability emerge naturally from the learning process. This approach provides a transparent, data-driven foundation for developing predictive molecular models and enhances confidence in computational descriptions of biophysical systems. We demonstrate the method using 18 biologically relevant molecular fragments that capture key motifs in proteins, nucleic acids, and lipids, and, as a proof of concept, apply it to calcium binding to troponin - a central event in cardiac regulation.

physics.chem-ph↗

arXiv2025

Experimental Evidence of Quantum Drude Oscillator Behavior in Liquids Revealed with Probabilistic Iterative Boltzmann Inversion

The first experimental evidence of quantum Drude oscillator behavior in liquids is determined using probabilistic machine learning-augmented iterative Boltzmann inversion applied to noble gas radial distribution functions. Furthermore, classical force fields for noble gases are shown to be reduced to a single parameter through simple empirical relations linked to atomic dipole polarizability. These findings highlight how neutron scattering data can inspire innovative force field design and offer insight into interatomic forces to advance molecular simulations.

physics.chem-ph↗

arXiv2023

Hydration of biologically relevant tetramethylammonium cation by neutron scattering and molecular dynamics

Neutron scattering and molecular dynamics studies were performed on a concentrated aqueous tetramethylammonium (TMA) chloride solution to gain insight into the hydration shell structure of TMA, which is relevant for understanding its behavior in biological contexts of, e.g., properties of phospholipid membrane headgroups or interactions between DNA and histones. Specifically, neutron diffraction with isotopic substitution experiments were performed on TMA and water hydrogens to extract the specific correlation between hydrogens in TMA ($\mathrm{H_{TMA}}$) and hydrogens in water ($\mathrm{H_{W}}$). Classical molecular dynamics simulations were performed to help interpret the experimental neutron scattering data. Comparison of the hydration structure and simulated neutron signals obtained with various force field flavors (e.g. overall charge, charge distribution, polarity of the CH bonds and geometry) allowed us to gain insight into how sensitive the TMA hydration structure is to such changes and how much the neutron signal can capture them. We show that certain aspects of the hydration, such as the correlation of the hydrogen on TMA to hydrogen on water, showed little dependence on the force field. In contrast, other correlations, such as the ion-ion interactions, showed more marked changes. Strikingly, the neutron scattering signal cannot discriminate between different hydration patterns. Finally, ab initio molecular dynamics was used to examine the three-dimensional hydration structure and thus to benchmark force field simulations. Overall, while neutron scattering has been previously successfully used to improve force fields, in the particular case of TMA we show that it has only limited value to fully determine the hydration structure, with other techniques such as ab initio MD being of a significant help.

physics.chem-ph↗

arXiv2023

Common Cations are not Polarizable: Effects of Dispersion Correction on Hydration Structures from Ab Initio Molecular Dynamics

We employed density functional theory-based ab initio molecular dynamics simulations to examine the hydration structure of several common alkali and alkali earth metal cations. We found that the commonly used atom pairwise dispersion correction scheme D3, which assigns dispersion coefficients based on the neutral form of the atom rather than its actual oxidation state, leads to inaccuracies in the hydration structures of these cations. We evaluated this effect for lithium, sodium, potassium, and calcium and found that the inaccuracies are particularly pronounced for sodium and potassium compared to the experiment. To remedy this issue, we propose disabling the D3 correction specifically for all cation-including pairs, which leads to a much better agreement with experimental data.

physics.chem-ph↗

arXiv2023

Non-Aqueous Ion Pairing Exemplifies the Case for Including Electronic Polarization in Molecular Dynamics Simulations

The inclusion of electronic polarization is of crucial importance in molecular simulations of systems containing charged moieties. When neglected, as often done in force field simulations, charge-charge interactions in solution may become severely overestimated leading to unrealistically strong bindings of ions to biomolecules. The electronic continuum correction introduces electronic polarization in a mean-field way via scaling of charges by the reciprocal of the square root of the high-frequency dielectric constant of the solvent environment. Here, we use ab initio molecular dynamics simulations to quantify the effect of electronic polarization on pairs of like-charged ions in a model non-aqueous environment where electronic polarization is the only dielectric response. Our findings confirm the conceptual validity of the present approach, underlining its applicability to complex aqueous biomolecular systems. Simultaneously, the present results justify the potential employment of weaker charge scaling factors in force field development.

physics.chem-ph↗

arXiv2022

Bridging Electrochemistry and Photoelectron Spectroscopy in the Context of Birch Reduction: Detachment Energies and Redox Potentials of Electron, Dielectron, and Benzene Radical Anion in Liquid Ammonia

Birch reduction is a time-proven way to hydrogenate aromatic hydrocarbons (such as benzene), which relies on the reducing power of electrons released from alkali metals into liquid ammonia. We have succeeded to characterize the key intermediates of the Birch reduction process - the solvated electron and dielectron and the benzene radical anion - using cyclic voltammetry and photoelectron spectroscopy, aided by electronic structure calculations. In this way, we not only quantify the electron binding energies of these species, which are decisive for the mechanism of the reaction but also use Birch reduction as a case study to directly connect the two seemingly unrelated experimental techniques.

physics.chem-ph↗

arXiv2021

Electronic Structure of the Solvated Benzene Radical Anion

The benzene radical anion is a molecular ion pertinent to several organic reactions, including the Birch reduction of benzene in liquid ammonia. The species exhibits a dynamic Jahn-Teller effect due to its open-shell nature and undergoes pseudorotation of its geometry. Here we characterize the complex electronic structure of this condensed-phase system based on ab initio molecular dynamics simulations and GW calculations of the benzene radical anion solvated in liquid ammonia. Using detailed analysis of molecular and electronic structure, we find that the spatial character of the excess electron of the solvated radical anion follows the underlying Jahn-Teller distortions of the molecular geometry. We decompose the electronic density of states to isolate the contribution of the solute and to examine the response of the solvent to its presence. Our findings show the correspondence between instantaneous molecular structure and spin density, provide important insights into the electronic stability of the species, revealing that it is indeed a bound state in the condensed phase, and offer electronic densities of states that aid in the interpretation of experimental photoelectron spectra.

physics.chem-ph↗

arXiv2021

Benzene Radical Anion Microsolvated in Ammonia Clusters: Modelling the Transition from an Unbound Resonance to a Bound Species

The benzene radical anion, well-known in organic chemistry as the first intermediate in the Birch reduction of benzene in liquid ammonia, exhibits intriguing properties from the point of view of quantum chemistry. Notably, it has the character of a metastable shape resonance in the gas phase, while measurements in solution find it to be experimentally detectable and stable. In this light, our previous calculations performed in bulk liquid ammonia explicitly reveal that solvation leads to stabilization. Here, we focus on the transition of the benzene radical anion from an unstable gas-phase ion to a fully solvated bound species by explicit ionization calculations of the radical anion solvated in molecular clusters of increasing size. The computational cost of the largest systems is mitigated by combining density functional theory with auxiliary methods including effective fragment potentials or approximating the bulk by polarizable continuum models. Using this methodology, we obtain the cluster size dependence of the vertical binding energy of the benzene radical anion converging to the value of $-$2.3 eV at a modest computational cost.

physics.chem-ph↗

arXiv2020

Guanidinium can both Cause and Prevent the Hydrophobic Collapse of Biomacromolecules

A combination of Fourier transform infrared and phase transition measurements as well as molecular computer simulations, and thermodynamic modeling were performed to probe the mechanisms by which guanidinium salts influence the stability of the collapsed versus uncollapsed state of an elastin-like polypeptide (ELP), an uncharged thermoresponsive polymer. We found that the cation's action was highly dependent upon the counteranion with which it was paired. Specifically, Gnd+ was depleted from the ELP/water interface and was found to stabilize the collapsed state of the macromolecule when paired with well-hydrated anions such as sulfate. Stabilization in this case occurred via an excluded volume (or depletion) effect, whereby sulfate was strongly partitioned away from the ELP/water interface. Intriguingly, at low salt concentrations, Gnd+ was also found to stabilize the collapsed state of the ELP when paired with SCN-, which is a strong binder for the ELP. In this case, the anion and cation were both found to be enriched in the collapsed state of the polymer. The collapsed state was favored because the Gnd+ crosslinked the polymer chains together. Moreover, the anion helped partition Gnd+ to the polymer surface. At higher salt concentrations (>1.5 M), GndSCN switched to stabilizing the uncollapsed state because a sufficient amount of Gnd+ and SCN- partitioned to the polymer surface to prevent cross-linking from occurring. Finally, in a third case, it was found that salts which interacted in an intermediate fashion with the polymer (e.g. GndCl) favored the uncollapsed conformation at all salt concentrations.

cond-mat.soft↗

arXiv2020

Benzene radical anion in the context of the Birch reduction: when solvation is the key

The benzene radical anion is an important intermediate in the Birch reduction of benzene by solvated electrons in liquid ammonia. Beyond organic chemistry, it is an intriguing subject of spectroscopic and theoretical studies due to its rich structural and dynamical behavior. In the gas phase, the species appears as a metastable shape resonance, while in the condensed phase it remains stable. Here, we approach the system by ab initio molecular dynamics in liquid ammonia and demonstrate that the inclusion of solvent is crucial and indeed leads to stability. Beyond the mere existence of the radical anion species, our simulations explore its condensed-phase behavior at the molecular level and offer new insights into its properties. These include the dynamic Jahn-Teller distortions, vibrational spectra in liquid ammonia, and the structure of the solvent shell, including the motif of a $π$-hydrogen bond between ammonia molecules and the aromatic ring.

physics.chem-ph↗