Aug 2026· Journal of Chemical Theory and Computation· Vol 22 16, pp.
8502-8520
· 0 citations· 42 references
Medicine
Abstract
We propose an improved model, termed the gradient-corrected PCM (GCPCM), for improving the energy accuracy of the polarizable continuum model (PCM). Our previous study revealed deficiencies of PCM in describing the reaction field, i.e., the electrostatic potential generated by the solvent. These deficiencies can be partially alleviated by introducing an empirical correction to the solvent charges. As a result, solute-solvent interactions are improved at the self-consistent field level, leading to enhanced energy accuracy. The performance of GCPCM was evaluated through single-point calculations and geometry optimizations of phenol and phenolate, calculations of the free energy profile for proton transfer in glycine, and analysis of solvent responses of the HOMO and LUMO orbital energies of Brooker's merocyanine. The results demonstrate that the characteristic destabilization of charged solutes observed in conventional PCM is effectively resolved. Furthermore, despite having a computational cost comparable to that of PCM, GCPCM shows the potential to achieve an energy accuracy similar to that of 3D-RISM-SCF. The development of GCPCM enables more convenient and accurate treatment of solvation effects, which is expected to allow researchers to focus on other important challenges, such as the accurate description of electronic states.
Accurate modeling of nonbonded interactions remains challenging because conventional force fields often provide inadequate descriptions of polarization and charge transfer. Here, we introduce a polarizable split-charge equilibration (PSQ) framework that combines localized charge flow with dipolar polarization, thereby mitigating the unphysical long-range charge delocalization associated with polarizable charge-equilibration models. To enable practical large-scale simulations, we develop an efficient PSQ implementation through algorithmic optimization and parallelization, achieving performance comparable to conventional approaches despite the model’s greater formal complexity. We combine PSQ with the universal nonbond potential for van der Waals interactions and an explicit four-body hydrogen-bond term to form the PUxH framework. PUxH achieves near-chemical accuracy in predicting small-molecular pair interactions and accurately reproduces the bulk properties of water, ammonia, and benzene. Overall, PUxH provides a transferable, physically grounded, and computationally efficient framework for modeling nonbonded interactions in molecular and condensed-phase systems.
Taehwan Jang, Minho M. Kim, Hoon Ryu et al.· Journal of Physical Chemistr...· 0 citations
The generalized PB theory is validated using a perturbed two-atom system and a diverse set of proteins with different structures in vacuum and water, demonstrating its accuracy and robustness, regardless of the choice of sharp-interface and diffuse-interface PB models and different numerical solvers.
Matthias Dogbatsey, Yuanzhen Shao, Emil Alexov et al.· 0 citations
We develop and validate a new united-atom (UA) model for alkylamines under the polarization consistent approach (PolCA) formalism. Making use of recent theoretical developments in the treatment of polarization effects, we apply post facto polarization corrections to improve the accuracy and transferability of the model. We parameterize the model against the experimental density, enthalpy of vaporization and dielectric constant of selected amine molecules. The model is then validated against self-solvation free energies and solvation free energies in n-hexadecane. Overall, the new PolCA model outperforms the state-of-the-art GROMOS UA model, eliminating systematic deviations in that model's predictions for methylamine. We also present further evidence that polarization energy corrections are required when transferring the model from pure liquids to mixtures, particularly when the solute and solvent have significantly different polarity. The main shortcoming of the model is the lack of accuracy in predictions of the dielectric constant of small amine molecules, which is overestimated relative to experimental data. We show that this is likely due to the effective dipole moment of practically all previous non-polarizable models (including PolCA) being higher than the real dipole moment of amines in the liquid phase, which we estimated using the recent Self-Consistent Electrostatic Embedding approach.
M. Barrera, J. R. Gomes, Miguel Jorge· Physical Chemistry, Chemical...· 0 citations
Solvent can reorganize reaction paths and barriers, but bringing those effects into mechanistic calculations remains expensive, because every image in a solvated climbing-image nudged elastic band search requires a new self-consistent reaction-field calculation. Here, we present a high-fidelity surrogate framework that keeps a preconstructed nonsolvated reaction valley as the backbone and models only the geometry-dependent solvent contribution needed to transform it into the solution-phase potential of mean force, i.e., the solvent-shaped free-energy surface. Using uncertainty-selected evaluations with the plane-wave implicit solvation model based on electron density (PW-SMD), the method optimizes solvated reaction paths on the fly and recovers 300 K free-energy profiles from local surrogate Hessians. For 16 small-molecule reactions in water and 17 Cu(111) interfacial reactions, the framework reduces the average number of solvent-response calculations from 826.3 to 67.3 and from 1231.9 to 51.5, respectively, while maintaining small-molecule barrier differences of only 0.04 eV on average and an interfacial reaction barrier agreement within a few hundredths of an eV for most reactions. The surrogate also reproduces representative room-temperature activation and reaction free energies. These results show that solvent-induced reshaping of reaction pathways can be captured accurately from a sparse, strategically chosen set of solution-phase calculations, turning solvated reaction-path and free-energy calculations into a practical tool for molecular and interfacial mechanistic studies.
Tevin Li, Junwei Lucas Bao· Journal of Chemical Theory a...· 0 citations
The self-consistent incorporation of Generalized Born (GB) model into the restriction-based configuration interaction long-range corrected density functional tight binding (RCI-LC-DFTB) framework enables a state-specific description of solvent polarization effects in photoinduced charge-separated (CS) states. In this scheme, the GB model contribution is constructed from the charge distribution of a selected target state and incorporated into the configuration interaction Hamiltonian through an effective one-electron operator, preserving the chemically intuitive interpretation of charge-localized diabatic configurations. We apply the method to two triphenylamine-naphthalene diimide (MTA-MNDI) donor-acceptor dyads connected by twisted phenylene-ethynylene bridges of different lengths. Our calculations demonstrate that solvent polarization significantly stabilizes the CS configuration, altering the energetic ordering between locally excited and CS states to thermodynamically drive charge separation. This approach offers a computationally efficient and chemically transparent framework for describing state-specific solvation and photophysical kinetics in large donor-acceptor assemblies.
Ji Huang, T. Kowalczyk, Daisuke Yokogawa· Journal of Chemical Theory a...· 0 citations
Ionic liquids are salts that exist in the liquid state at room temperature and exhibit high viscosity because of their strong electrostatic interactions. It was difficult to reproduce their viscosity by molecular dynamics simulations with conventional nonpolarizable force fields; however, recent development of force fields implementing electronic continuum correction (ECC), which accounts for polarizability, has enabled accurate predictions. Here, we present a regression-guided strategy to optimize scaling factors for ECC charges and Lennard-Jones parameters for monomeric (BMIM+, MOEMIM+) and oligomeric (IL22+, IL44+) imidazolium-based cations paired with TFSI– with united-atom models. The scaling factors were optimized to simultaneously reproduce experimental density and viscosity. To validate the strategy, we calculated the temperature dependence of density, diffusion coefficient, conductivity, and viscosity of BMIM–TFSI, achieving good agreements with experiments. Moreover, scaling factors optimized for MOEMIM+, which shares similar chemical structure and elemental compositions with IL22+ and IL44+, were found to be transferable to these compounds. Thus, this work not only provides a practical regression-guided workflow for selecting ECC-based united-atom force-field parameters but also suggests their transferability across chemically related ionic liquids.
