Journal of Chemical Theory and Computation最新文献

The Atomic Density-Based Tight-Binding (aTB) Model: A Robust and Accurate Semiempirical Method Parametrized for H-Ra; Applied to Structures, Vibrational Frequencies, Noncovalent Interactions, and Excited States.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-28 DOI: 10.1021/acs.jctc.4c01694

Yingfeng Zhang, Jin Xiao, Shunyu Wang, Tong Zhu, John Z H Zhang

引用次数: 0

Reaction Mechanism Path Sampling Based on Parallel Cascade Selection QM/MM Molecular Dynamics Simulation: PaCS-Q.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-28 DOI: 10.1021/acs.jctc.5c00169

Lian Duan, Kowit Hengphasatporn, Ryuhei Harada, Yasuteru Shigeta

{"title":"Reaction Mechanism Path Sampling Based on Parallel Cascade Selection QM/MM Molecular Dynamics Simulation: PaCS-Q.","authors":"Lian Duan, Kowit Hengphasatporn, Ryuhei Harada, Yasuteru Shigeta","doi":"10.1021/acs.jctc.5c00169","DOIUrl":"https://doi.org/10.1021/acs.jctc.5c00169","url":null,"abstract":"Quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations are essential for elucidating complex biochemical reaction mechanisms. However, conventional enhanced sampling methods, such as umbrella sampling and metadynamics, often face limitations in computational cost, sampling completeness, and reliance on predefined reaction coordinates. To address these challenges, we developed Parallel Cascade Selection QM/MM MD (PaCS-Q) simulation, a novel strategy that efficiently explores reaction pathways by iteratively identifying high-potential structures for configurational transitions without predefined biases or external constraints. PaCS-Q directly tracks changes in bond distances over time, enabling the identification of transition states and intermediates. Validation of the Claisen rearrangement in chorismate mutase and the peptidyl aldehyde reaction in the Zika virus NS2B/NS3 serine protease demonstrated accurate pathway capture, reduced computational costs, and efficient sampling. With its user-friendly workflow, PaCS-Q broadens accessibility for computational and experimental researchers, offering a robust tool for studying enzymatic mechanisms with high accuracy and efficiency.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plateaus in the Potentials of Density-Functional Theory: Analytical Derivation and Useful Approximations.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-27 DOI: 10.1021/acs.jctc.4c01771

Nathan E Rahat, Eli Kraisler

{"title":"Plateaus in the Potentials of Density-Functional Theory: Analytical Derivation and Useful Approximations.","authors":"Nathan E Rahat, Eli Kraisler","doi":"10.1021/acs.jctc.4c01771","DOIUrl":"https://doi.org/10.1021/acs.jctc.4c01771","url":null,"abstract":"Density functional theory (DFT) is an extremely efficient and widely used method for electronic structure calculations. However, the quality of such calculations crucially depends on the quality of the approximation used for the exchange-correlation functional, for which there is no exact form. One important feature of the exact exchange-correlation potential, which common approximations usually do not capture, is the spatial steps and plateaus that occur in various scenarios, including ionization, excitation, dissociation, and charge transfer. In this paper, we derive an analytical expression for the plateau in the Kohn-Sham potential that forms around the center of the system, when the number of electrons infinitesimally surpasses an integer. The resulting formula is the first analytical expression of its kind. The derivation is performed using the orbital-free DFT framework, analyzing both the Kohn-Sham-Pauli and the Pauli potentials. Analytical results are compared to exact calculations for small atomic systems, showing close correspondence and high accuracy. Furthermore, it is shown that plateaus can be produced also when relying on approximate electron densities, even those obtained with the simplest exchange-correlation form─the local density approximation.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeted Transferable Machine-Learned Potential for Linear Alkanes Trained on C₁₄H₃₀ and Tested for C₄H₁₀ to C₃₀H₆₂.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-27 DOI: 10.1021/acs.jctc.4c01793

Chen Qu, Paul L Houston, Thomas Allison, Joel M Bowman

{"title":"Targeted Transferable Machine-Learned Potential for Linear Alkanes Trained on C14H30 and Tested for C4H10 to C30H62.","authors":"Chen Qu, Paul L Houston, Thomas Allison, Joel M Bowman","doi":"10.1021/acs.jctc.4c01793","DOIUrl":"https://doi.org/10.1021/acs.jctc.4c01793","url":null,"abstract":"Given the great importance of linear alkanes in fundamental and applied research, an accurate machine-learned potential (MLP) would be a major advance in computational modeling of these hydrocarbons. Recently, we reported a novel, many-body permutationally invariant model that was trained specifically for the 44-atom hydrocarbon C14H30 on roughly 250,000 B3LYP energies (Qu, C.; Houston, P. L.; Allison, T.; Schneider, B. I.; Bowman, J. M. J. Chem. Theory Comput. 2024, 20, 9339-9353). Here, we demonstrate the accuracy of the transferability of this potential for linear alkanes ranging from butane C4H10 up to C30H62. Unlike other approaches for transferability that aim for universal applicability, the present approach is targeted for linear alkanes. The mean absolute error (MAE) for energy ranges from 0.26 kcal/mol for butane and rises to 0.73 kcal/mol for C30H62 over the energy range up to 80 kcal/mol for butane and 600 kcal/mol for C30H62. These values are unprecedented for transferable potentials and indicate the high performance of a targeted transferable potential. The conformational barriers are shown to be in excellent agreement with high-level ab initio calculations for pentane, the largest alkane for which such calculations have been reported. Vibrational power spectra of C30H62 from molecular dynamics calculations are presented and briefly discussed. Finally, the evaluation time for the potential is shown to vary linearly with the number of atoms.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Activity-Induced Droplet Inversion in Multicomponent Liquid-Liquid Phase Separation.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-26 DOI: 10.1021/acs.jctc.5c00162

Xianyun Jiang, Zhonghuai Hou

{"title":"Activity-Induced Droplet Inversion in Multicomponent Liquid-Liquid Phase Separation.","authors":"Xianyun Jiang, Zhonghuai Hou","doi":"10.1021/acs.jctc.5c00162","DOIUrl":"https://doi.org/10.1021/acs.jctc.5c00162","url":null,"abstract":"Liquid-liquid phase separation (LLPS) is a vital process in forming membrane-free organelles, crucial for cell physiology and recently gaining significant attention. However, the effects of nonequilibrium factors, which are common in real life, on the process of LLPS have not been fully explored. To address this issue, we developed a model for nonequilibrium phase separation involving three components (A, B, and C) by integrating a nonequilibrium term into the chemical potential for active component B. We find significant changes in the morphology and dynamics of nonequilibrium phase-separated droplets compared to their equilibrium counterparts. Remarkably, with a large enough activity, the B-A-C structure (B at the center, surrounded by A, then enveloped by C) under equilibrium conditions may change to a C-A-B structure. Further simulations give a global picture of the system under both active and passive conditions, revealing the shifts of the phase boundaries and unraveling the effect of activity on different droplet structures. We derived an effective free energy for the active LLPS system to provide a qualitative understanding of our observations. Our study presents a basic model for nonequilibrium phase separation processes, providing crucial insights into LLPS alongside intracellular nonequilibrium phenomena.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Accurate and Rapid Prediction of Protein pK_a: Protein Language Models Reveal the Sequence-pK_a Relationship.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-26 DOI: 10.1021/acs.jctc.4c01288

Shijie Xu, Akira Onoda

{"title":"Accurate and Rapid Prediction of Protein pKa: Protein Language Models Reveal the Sequence-pKa Relationship.","authors":"Shijie Xu, Akira Onoda","doi":"10.1021/acs.jctc.4c01288","DOIUrl":"https://doi.org/10.1021/acs.jctc.4c01288","url":null,"abstract":"Protein pKa prediction is a key challenge in computational biology. In this study, we present pKALM, a novel deep learning-based method for high-throughput protein pKa prediction. pKALM uses a protein language model (PLM) to capture the complex sequence-structure relationships of proteins. While traditionally considered a structure-based problem, our results show that a PLM pretrained on large-scale protein sequence databases can effectively learn this relationship and achieve state-of-the-art performance. pKALM accurately predicts the pKa values of six residues (Asp, Glu, His, Lys, Cys, and Tyr) and two termini with high precision and efficiency. It performs well at predicting both exposed and buried residues, which often deviate from standard pKa values measured in the solvent. We demonstrate a novel finding that predicted protein isoelectric points (pI) can be used to improve the accuracy of pKa prediction. High-throughput pKa prediction of the human proteome using pKALM achieves a speed of 4,965 pKa predictions per second, which is several orders of magnitude faster than existing state-of-the-art methods. The case studies illustrate the efficacy of pKALM in estimating pKa values and the constraints of the method. pKALM will thus be a valuable tool for researchers in the fields of biochemistry, biophysics, and drug design.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Going beyond the Computational Tool: Fermi Potential from DFT as an Electron (De)Localization Descriptor for Correlated Wave Functions.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-26 DOI: 10.1021/acs.jctc.4c01745

Elena O Levina, Vladimir G Tsirelson

{"title":"Going beyond the Computational Tool: Fermi Potential from DFT as an Electron (De)Localization Descriptor for Correlated Wave Functions.","authors":"Elena O Levina, Vladimir G Tsirelson","doi":"10.1021/acs.jctc.4c01745","DOIUrl":"https://doi.org/10.1021/acs.jctc.4c01745","url":null,"abstract":"The Fermi potential, appearing in the basic equations of density functional theory (DFT), has been found to be an indispensable tool for the measurement of electron localization intensity in molecules and crystals. The regions of the most intensive electron localization appear there as negative wells, while the positive barriers of the Fermi potential prevent the electron concentration there to some extent. The shape of the Fermi potential distribution in covalent bonds reflects the bond order, while the structure of its components is able to provide valuable information about the bonding nature, e.g., helping to draw the line between covalent and noncovalent bonds. The accuracy of the Fermi potential's estimates of electron (de)localization stems from the ability of its components to preserve all the main features of the exchange-correlation hole behavior within the one-electron functions, while other popular descriptors can easily fail in this task. Such analysis is not restricted to DFT calculations; when applied to post-Hartree-Fock wave functions, it unravels details of how instantaneous Coulomb correlation prevents the overestimation of electron localization intensity in strongly correlated and ordinary systems. Generally, the slight decrease in localization intensity is achieved by the intensified response of electron correlation to variations in electron density, while in systems where instantaneous Coulomb correlation is particularly important, it also comes from the growth in the exchange-correlation hole mobility; the average hole depth increases in all cases.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Simple Linear Regression Models for Prediction of Ionization Energies, Electron Affinities, and Fundamental Gaps of Atoms and Molecules.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-26 DOI: 10.1021/acs.jctc.4c01591

Rebecca K Carlson

引用次数: 0

Simulations of Two-Photon Absorption Spectra of Fluorescent Dyes: The Impact of Non-Condon Effects.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-26 DOI: 10.1021/acs.jctc.4c01545

Rudraditya Sarkar, Carmelo Naim, Karan Ahmadzadeh, Robert Zaleśny, Denis Jacquemin, Josep M Luis

{"title":"Simulations of Two-Photon Absorption Spectra of Fluorescent Dyes: The Impact of Non-Condon Effects.","authors":"Rudraditya Sarkar, Carmelo Naim, Karan Ahmadzadeh, Robert Zaleśny, Denis Jacquemin, Josep M Luis","doi":"10.1021/acs.jctc.4c01545","DOIUrl":"https://doi.org/10.1021/acs.jctc.4c01545","url":null,"abstract":"Computer simulations play a pivotal role in interpreting experimental two-photon absorption (2PA) spectra. One of the key aspects of the simulation of these spectra is to take into account the vibrational fine structure of the bands in electronic spectra. This is typically done by employing Franck-Condon (FC) term and low-order terms in the Herzberg-Teller (HT) expansion. In this work, we present a systematic study of first-order HT effects on the vibronic structure of π → π* electronic bands in 2PA spectra of 13 common fluorophores. We begin by evaluating the performance of several density functional approximations (DFAs) against the second-order coupled cluster singles and doubles model (CC2) for reproducing two-photon transition moments and their first- and second-order derivatives with respect to normal modes of vibration on a set of six donor-acceptor molecules. Our findings reveal that most DFAs produce inaccurate values for these derivatives, with the exception of the LC-BLYP functionals with range-separation parameters of 0.33 and 0.47. Although these functionals underestimate the HT contribution to the 2PA total intensities of the π → π* electronic bands, they offer a reasonable qualitative reproduction of the HT vibrational fine structure of the reference spectra. We further explore HT effects on fluorescent chromophores, finding that HT contributions are secondary to FC effects, leading to small shifts of the wavelengths peaks, and minimal changes in the intensities. Additionally, the adiabatic Hessian, vertical Hessian, and vertical gradient vibronic models are assessed. The general agreement among these models confirms that the harmonic approximation is suitable for studying the selected fluorophores.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessment of the Topology and Oligomerisation States of Coiled Coils Using Metadynamics with Conformational Restraints.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-25 Epub Date: 2025-03-05 DOI: 10.1021/acs.jctc.4c01695

Evangelia Notari, Christopher W Wood, Julien Michel

{"title":"Assessment of the Topology and Oligomerisation States of Coiled Coils Using Metadynamics with Conformational Restraints.","authors":"Evangelia Notari, Christopher W Wood, Julien Michel","doi":"10.1021/acs.jctc.4c01695","DOIUrl":"10.1021/acs.jctc.4c01695","url":null,"abstract":"Coiled-coil proteins provide an excellent scaffold for multistate de novo protein design due to their established sequence-to-structure relationships and ability to switch conformations in response to external stimuli, such as changes in pH or temperature. However, the computational design of multistate coiled-coil protein assemblies is challenging, as it requires accurate estimates of the free energy differences between multiple alternative coiled-coil conformations. Here, we demonstrate how this challenge can be tackled using metadynamics simulations with orientational, positional and conformational restraints. We show that, even for subtle sequence variations, our protocol can predict the preferred topology of coiled-coil dimers and trimers, the preferred oligomerization states of coiled-coil dimers, trimers, and tetramers, as well as the switching behavior of a pH-dependent multistate system. Our approach provides a method for predicting the stability of coiled-coil designs and offers a new framework for computing binding free energies in protein-protein and multiprotein complexes.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"3260-3276"},"PeriodicalIF":5.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0