Assessing the Partial Hessian Approximation in QM/MM-Based Vibrational Analysis DOI Creative Commons
Jonas Vester, Jógvan Magnus Haugaard Olsen

Journal of Chemical Theory and Computation, Journal Year: 2024, Volume and Issue: 20(21), P. 9533 - 9546

Published: Oct. 18, 2024

The partial Hessian approximation is often used in vibrational analysis of quantum mechanics/molecular mechanics (QM/MM) systems because calculating the full matrix computationally impractical. This approach aligns with core concept QM/MM, which focuses on QM subsystem. Thus, using implies that main interest local modes Here, we investigate accuracy and applicability (PHVA) as it typically within i.e., only belonging to subsystem computed. We focus solute-solvent small, rigid solutes. To separate two major sources errors, perform analyses. First, study effects normal modes, harmonic frequencies, IR Raman intensities by comparing them those obtained Hessians, where both Hessians are calculated at level. Then, quantify errors introduced QM/MM PHVA a QM/MM-type embedding Another aspect appearance resembling translation rotation These pseudotranslational pseudorotational should be removed they collective vibrations atoms relative frozen MM and, thus, not well-described. show projecting out rotation, usually done for isolation, can adversely affect other modes. Instead, identified removed.

Language: Английский

Nuclear Quantum Effects and the Grotthuss Mechanism Dictate the pH of Liquid Water DOI
Saswata Dasgupta, Giuseppe Cassone, Francesco Paesani

et al.

The Journal of Physical Chemistry Letters, Journal Year: 2025, Volume and Issue: unknown, P. 2996 - 3003

Published: March 16, 2025

Water's ability to autoionize into hydronium (H3O+) and hydroxide (OH–) ions dictates the acidity or basicity of aqueous solutions, influencing reaction pathways many chemical biochemical processes. In this study, we determine molecular mechanism autoionization process by leveraging both computational efficiency a deep neural network potential trained on highly accurate data calculated within density-corrected density functional theory enhanced sampling techniques ensure comprehensive exploration underlying multidimensional free-energy landscape. By properly accounting for nuclear quantum effects, our simulations provide an estimate constant liquid water (pKw = 13.71 ± 0.16), offering realistic molecular-level picture emphasizing its quantum-mechanical nature. Importantly, highlight central role played Grotthuss in stabilizing solvent-separated ion pair configurations, revealing profound impact acid–base equilibria environments.

Language: Английский

Citations

3
Quick-and-Easy Validation of Protein–Ligand Binding Models Using Fragment-Based Semiempirical Quantum Chemistry DOI
Paige E. Bowling, Dustin R. Broderick, John M. Herbert

et al.

Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Electronic structure calculations in enzymes converge very slowly with respect to the size of model region that is described using quantum mechanics (QM), requiring hundreds atoms obtain converged results and exhibiting substantial sensitivity (at least smaller models) which amino acids are included QM region. As such, there considerable interest developing automated procedures construct a based on well-defined criteria. However, testing such burdensome due cost large-scale electronic calculations. Here, we show semiempirical methods can be used as alternatives density functional theory (DFT) assess convergence sequences models generated by various protocols. The these tests reduced even further means many-body expansion. We use this approach examine (with size) protein–ligand binding energies. Fragment-based afford well-converged interaction energies tiny fraction required for DFT Two-body interactions between ligand single-residue acid fragments low-cost way "QM-informed" enzyme size, furnishing an automatable active-site model-building procedure. This provides streamlined, user-friendly constructing binding-site requires neither priori information nor manual adjustments. Extension thermochemical should straightforward.

Language: Английский

Citations

2
Predicting Carbonic Anhydrase Binding Affinity: Insights from QM Cluster Models DOI
Mackenzie Taylor,

Haedam Mun,

Junming Ho

et al.

The Journal of Physical Chemistry B, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

A systematic series of QM cluster models has been developed to predict the trend in carbonic anhydrase binding affinity a structurally diverse dataset ligands. Reference DLPNO–CCSD(T)/CBS energies were generated for model and used evaluate performance contemporary density functional theory methods, including Grimme's "3c" DFT composite methods (r2SCAN-3c ωB97X-3c). It is demonstrated that when validated are used, predictive power improves systematically with size models. This provided valuable insights into key interactions need be modeled quantum mechanically could inform how region should defined hybrid mechanics/molecular mechanics (QM/MM) The use r2SCAN-3c on largest composed 16 residues appears an economical approach predicting trends compared using more robust such as ωB97M-V provides significant improvement docking.

Language: Английский

Citations

0
Testing a Heterogeneous Polarizable Continuum Model against Exact Poisson Boundary Conditions DOI
Paige E. Bowling, Montgomery Gray,

Suranjan K. Paul

et al.

Journal of Chemical Theory and Computation, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

The polarizable continuum model (PCM) is a computationally efficient way to incorporate dielectric boundary conditions into electronic structure calculations, via boundary-element reformulation of Poisson's equation. This transformation only rigorously valid for an isotropic medium. To simulate anisotropic solvation, as encountered at interface or when parts system are solvent-exposed while other in nonpolar environment, ad hoc modifications the PCM formalism have been suggested, which constant assigned separately each atomic sphere that contributes solute cavity. accuracy this "heterogeneous" (HetPCM) method tested here first time, by comparison results from generalized Poisson equation solver. latter more expensive and cumbersome approach arbitrary conditions, but one corresponds well-defined scalar permittivity function, ε(r). We examine simple systems function ε(r) can be constructed manner maps reasonably well onto sphere, using εsolv = 78 range smaller values represent hydrophobic environments. For constants εnonp ≤ 2, differences between HetPCM solvation energies large compared effect anisotropy on energy. 4 10, however, agree within 2 kcal/mol most cases. As realistic use case, we apply predict pKa blue copper proteins. affords line with experimental either gas-phase calculations homogeneous (isotropic) results.

Language: Английский

Citations

0
Long-Lived Intramolecular Charge Transfer in Persubstituted Perylenediimide DOI
Anjana V. Muralidharan, Kavya Vinod, Fathima Thasnim Pattanmarthodiyil

et al.

The Journal of Physical Chemistry C, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Photoinduced charge transfer (CT) states play a pivotal role in increasing the power conversion efficiency of molecular systems used artificial photosynthesis, photocatalysis, and optronic devices. The absence intrinsic CT is one main reasons for poor photoconversion efficiencies organic chromophores like perylenediimide (PDI). Herein, we explore excited state dynamics persubstituted PDI (AP) with amino groups at ortho positions bromine atoms bay positions. Due to influence on core, nonradiative pathways are accessed photoexcitation AP. Femtosecond nanosecond transient absorption measurements weakly polar solvents showed relaxation higher singlet picoseconds time scale, paving way an intramolecular (ICT) having lifetime nanoseconds scale. As dielectric medium changed from solvent (toluene, ε = 2.38) (ethyl acetate, 6.02), stabilized decreased τ 69.1 ± 1.7 ns 47.1 0.5 ns, which confirms dependency ICT state. Theoretical investigations employing surface hopping suggest that rate internal (kIC 1.13 × 1011 s–1) competes intersystem crossing (kISC 0.85 Amination position induces characteristics core PDI, as evident hole–electron analysis S1 Presented results long-lived relaxed may improve designing strategies optoelectronic

Language: Английский

Citations

0
Adaptive Restraints to Accelerate Geometry Optimizations of Large Biomolecular Systems DOI
Mark A. Hix, Alice R. Walker

Journal of Computational Chemistry, Journal Year: 2025, Volume and Issue: 46(12)

Published: May 3, 2025

ABSTRACT Quantum mechanical/molecular mechanical geometry optimizations of large‐scale biological systems, such as enzymes, proteins, membranes, and solutions, are typically computationally expensive to the point being cost‐prohibitive. By convention, an approximation is made calculations that atoms beyond a certain distance from QM region provide only negligible improvements resulting optimization energy geometry, restrained reduce number degrees freedom. These constraints normally applied user‐defined radius. Here we describe new method acceleration automation which generates adaptive gradient‐based restraints for QM/MM optimizations, leading significantly faster generally lower relative energies. The determined by algorithm rather than user, can adapt directional well differences in starting geometry. This flexibility key finding excited state minima minimum conical intersections (MECIs) complex protein environments. was implemented external Python tool use alongside TeraChem, with modular interface be straightforwardly other packages. We tested on green fluorescent (rsEGFP2) two red proteins (FusionRed, mScarlet) water proton‐swapping aspartic acid pair explicit water. able produce nearly 50% reduction computational time while maintaining appropriately optimized geometries

Language: Английский

Citations

0
Nuclear quantum effects and the Grotthuss mechanism dictate the pH of liquid water DOI Creative Commons
Saswata Dasgupta, Giuseppe Cassone, Francesco Paesani

et al.

Published: Aug. 27, 2024

Water’s ability to autoionize into hydronium (H3O+) and hydroxide (OH−) ions dictates the acidity or basicity of aqueous solutions, influencing reaction pathways many chemical biochemical processes. In this study, we determine molecular mechanism autoionization process by leveraging both computational efficiency a deep neural network potential trained on highly accurate data calculated within density-corrected density functional theory enhanced sampling techniques ensure comprehensive exploration underlying multidimensional free- energy landscape. By properly accounting for nuclear quantum effects, our simulations provide an estimate constant liquid water (pKw = 13.71 ± 0.16), offering realistic molecular-level picture emphasizing its quantum-mechanical nature. Importantly, highlight central role played Grotthuss in stabilizing solvent-separated ion pair configurations, revealing profound impact acid-base equilibria environments.

Language: Английский

Citations

1
Quantum Chemical Studies of the Reaction Mechanisms of Enzymatic CO2 Conversion DOI
B. X. Liu,

Beibei Lin,

Hao Su

et al.

Physical Chemistry Chemical Physics, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Enzymatic capture and conversion of carbon dioxide (CO 2 ) into value-added chemicals are great interest in the field biocatalysis have a positive impact on climate change.

Language: Английский

Citations

1
Assessing the Partial Hessian Approximation in QM/MM-Based Vibrational Analysis DOI Creative Commons
Jonas Vester, Jógvan Magnus Haugaard Olsen

Journal of Chemical Theory and Computation, Journal Year: 2024, Volume and Issue: 20(21), P. 9533 - 9546

Published: Oct. 18, 2024

The partial Hessian approximation is often used in vibrational analysis of quantum mechanics/molecular mechanics (QM/MM) systems because calculating the full matrix computationally impractical. This approach aligns with core concept QM/MM, which focuses on QM subsystem. Thus, using implies that main interest local modes Here, we investigate accuracy and applicability (PHVA) as it typically within i.e., only belonging to subsystem computed. We focus solute-solvent small, rigid solutes. To separate two major sources errors, perform analyses. First, study effects normal modes, harmonic frequencies, IR Raman intensities by comparing them those obtained Hessians, where both Hessians are calculated at level. Then, quantify errors introduced QM/MM PHVA a QM/MM-type embedding Another aspect appearance resembling translation rotation These pseudotranslational pseudorotational should be removed they collective vibrations atoms relative frozen MM and, thus, not well-described. show projecting out rotation, usually done for isolation, can adversely affect other modes. Instead, identified removed.

Language: Английский

Citations

1