Aug 2026· Journal of Physical Chemistry B· Vol 130 34, pp.
8710-8723
· 0 citations· 91 references
Medicine
Abstract
Solvation free energy (SFE) is a fundamental thermodynamic quantity governing biomolecular processes in solution. Although the atomic decomposition method derived from the Kirkwood charging formula enables site-resolved evaluation of SFE contributions, its application within the three-dimensional reference interaction site model (3D-RISM) theory suffers from systematic overestimation relative to benchmark values. Here, we developed the Multi-Input Linear Correction for Atomic Decomposition (MILC-AD) framework by extending the original MILC approach to the atomic decomposition scheme within 3D-RISM theory. Unlike the original MILC framework, which relies on the nondecomposable partial molar volume (PMV), the proposed method uses atomically decomposable solute-solvent interaction energies as descriptors. Validated against 628 molecules from the benchmark FreeSolv database, the framework achieves a mean absolute deviation (MAD) of 0.57 kcal/mol relative to the Bennett acceptance ratio (BAR) calculations using ensemble-averaged predictions over ten conformations per molecule. As a representative application, the method is applied to the 36-residue villin headpiece subdomain HP36, revealing the site-resolved balance between intramolecular packing, SFE, and solvation entropy underlying the cooperative assembly of its hydrophobic core. These results demonstrate the potential of the MILC-AD framework as a practical tool for quantitative, site-resolved thermodynamic analyses of complex biomacromolecular systems.
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
We investigated the energetics and bonding of lithium hydride clusters (LiH)n (n = 1-6) using a composite ab initio scheme inspired by W2 theory to achieve sub-kcal/mol accuracy. This approach combines CCSD(T) results extrapolated to the complete basis set limit with a rigorous treatment of core-valence correlation, scalar relativistic effects, and the diagonal Born-Oppenheimer correction. Our results show that while Hartree-Fock theory captures the primary electrostatic binding, correlation effects are crucial for determining the energetic preference of compact isomers over cyclic rings. A parallel density functional theory study shows that while standard hybrid functionals like B3LYP-D4 and M06-2X exhibit larger deviations, the double-hybrid revDSD-PBEP86-D4 functional closely matches our benchmarks, delivering sub-kcal/mol accuracy. Structural and chemical bonding analyses, including intrinsic bond orbital, nucleus-independent chemical shift, and many-body expansion (MBE) methods, reveal high ionic character and multi-center bonding (3c-2e and 4c-2e) within the (LiH)n clusters. MBE analysis of the interaction energy of the monocyclic clusters with respect to the LiH molecules reveals that the two- and three-body terms are consistently negative (stabilizing), while all higher-order terms are negligible. We find that σ-aromaticity in these systems is predominantly local and bond-centered. As the rings expand, the interior becomes magnetically decoupled from the σ-skeleton, precluding the formation of a global ring current. These results establish definitive benchmarks for the stability of prototypical electron-deficient clusters.
Emmanouil C. Semidalas, Filippos Drakopoulos, E. A. Routsi et al.· Journal of Chemical Physics· 0 citations
Core–valence (CV) correlation causes systematic milliangstrom-scale bond contractions in main-group molecules. We develop an analytic radial model for the structural all-electron–frozen-core (AE–FC) correction otherwise obtained from explicit second-order Møller–Plesset perturbation theory (MP2) calculations. Calibrated once at the MP2/cc-pwCVTZ level, the model can be applied to geometries generated with different FC parent methods. The data set comprises 11 atomic references, 91 molecular systems, 145 radial scans, 116 angular scans, and 9966 molecular geometries with paired AE and FC energies. After atomic-reference subtraction, radial profiles are accurately described by A + B exp(Cr), whereas angular profiles are much smaller near equilibrium and serve as validation data. The model therefore targets the geometry-driving CV response rather than the full CV energy itself. The fitted field reproduces AE–FC bond shifts obtained from independent AE and FC optimizations with r = 0.973 and a root-mean-square residual of 0.512 mÅ. Analysis of the optimized geometries supports the reduction of bond-class parameters to additive atomic increments and reveals period- and group-dependent trends. The compressed correction transfers without refitting to larger held-out H/C/O molecules and enables direct transformation of FC into AE geometries without additional all-electron optimizations.
Unknown authors· Journal of Chemical Theory a...· 0 citations
The local potential energy (LPE) and local potential energy density (LPED) are Coulomb‐based QTAIM descriptors that assign interaction energies directly to individual bond critical points (BCPs), circumventing the locality limitation of global energy decomposition methods. Despite sharing the same algebraic expression, they differ by a single assumption—the zeroth‐order approximation—in which LPE implicitly sets the effective BCP volume to 1 Bohr
3
, collapsing LPED into an energy directly comparable to the supramolecular interaction energy (SME). Here, we provide the first rigorous derivation of this approximation, showing that its relative error is fully determined by |∇
2
ρ
bcp
|/
ρ
bcp
, yielding a mean of 13.38% ± 2.39% across 25 chemically diverse systems. Linear correlation analysis reveals LPED achieves
R
2
= 0.9607 with SME—marginally below
ρ
bcp
(
R
2
= 0.9701) yet substantially above VIR(bcp) (
R
2
= 0.8698), confirming that isolating the electron–nucleus attractive term enhances rather than degrades predictive performance. Quantitative benchmarking establishes clear, application‐dependent selection criteria for both descriptors.
The LDA-1/2 method provides an efficient correction to semilocal density functional theory for improving ionization energies and band gaps, yet its application to molecular systems has remained limited. In this work, we present an all-electron finite-element implementation of LDA-1/2 within the NESSIE electronic-structure framework and apply it to the GW100 molecular benchmark set with systematically controllable numerical accuracy. The self-energy correction is constructed explicitly from neutral and half-ionized calculations for each molecule, avoiding the use of precomputed atomic correction potentials. The real-space finite-element formulation enables systematic convergence with respect to the discretization and provides a controlled assessment of LDA-1/2 performance. For the GW100 set, the present implementation yields a mean absolute error of 0.472 eV and a root-mean-square error of 0.645 eV relative to CCSD(T) reference ionization energies, substantially improving upon conventional LDA and the previously reported LAPW implementation of LDA-1/2, while achieving accuracy comparable to G0W0@PBE. Convergence tests show that third-order finite elements are sufficient to reach or approach chemical accuracy relative to higher-order calculations for the representative systems considered. The resulting corrected Hamiltonian also improves several lower lying valence states relative to LDA, although the improvement becomes less systematic away from the HOMO. This work provides accurate LDA-1/2 benchmark data for molecular systems and establishes a rigorous finite-element foundation for future molecular GW calculations.
Dongming Li, Niamh Matthews, Qing-Chuan Sang et al.· 0 citations
A fast pipeline based on the OPLS-AA force field is presented that enables the automated calculation of non-bonding intermolecular (dimer) interaction energies derived from a set of small organic (monomer) molecules. To calculate the non-bonding contributions, optimized geometries of the monomer molecules as well as their OPLS-AA van der Waals and atomic partial charge parameters are required. The key advantage of the new pipeline lies in its fast, highly parallelized in-memory computations without slow I/O operations, which make it possible to thoroughly process comparatively large numbers of (more than a hundred) monomer molecules within acceptable time frames (hours and days): Compared to an analogous, more versatile, and comprehensive approach, the new computational scheme delivers comparable results while being more than two orders of magnitude faster. For locally estimating the required OPLS-AA force field parameters with the LigParGen and BOSS software packages, a user-friendly graphical user interface for the Windows operating system is provided. Scientific contribution Rapid calculation of mutual intermolecular energies for a set of monomer molecules based on the widely used OPLS-AA force field enables a considerable expansion of this type of calculation for practical purposes. The performance improvement can be used to achieve significant improvements of interaction energy averages as well as considerable expansions in the size of the monomer molecule set.
Mirco Daniel, Hannah Kullik, Martin Urban et al.· Journal of Cheminformatics· 0 citations
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