Journal of Chemical Theory and Computation最新文献_第9页

Unsupervised Learning of Progress Coordinates during Weighted Ensemble Simulations: Application to NTL9 Protein Folding.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-19 DOI: 10.1021/acs.jctc.4c01136

Jeremy M G Leung, Nicolas C Frazee, Alexander Brace, Anthony T Bogetti, Arvind Ramanathan, Lillian T Chong

{"title":"Unsupervised Learning of Progress Coordinates during Weighted Ensemble Simulations: Application to NTL9 Protein Folding.","authors":"Jeremy M G Leung, Nicolas C Frazee, Alexander Brace, Anthony T Bogetti, Arvind Ramanathan, Lillian T Chong","doi":"10.1021/acs.jctc.4c01136","DOIUrl":"10.1021/acs.jctc.4c01136","url":null,"abstract":"A major challenge for many rare-event sampling strategies is the identification of progress coordinates that capture the slowest relevant motions. Machine-learning methods that can identify progress coordinates in an unsupervised manner have therefore been of great interest to the simulation community. Here, we developed a general method for identifying progress coordinates \"on-the-fly\" during weighted ensemble (WE) rare-event sampling via deep learning (DL) of outliers among sampled conformations. Our method identifies outliers in a latent space model of the system's sampled conformations that is periodically trained using a convolutional variational autoencoder. As a proof of principle, we applied our DL-enhanced WE method to simulate the NTL9 protein folding process. To enable rapid tests, our simulations propagated discrete-state synthetic molecular dynamics trajectories using a generative, fine-grained Markov state model. Results revealed that our on-the-fly DL of outliers enhanced the efficiency of WE by >3-fold in estimating the folding rate constant. Our efforts are a significant step forward in the unsupervised learning of slow coordinates during rare event sampling.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655502","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

First-Principles Simulations of Molecular Optoelectronic Materials: Elementary Excitations and Spatiotemporal Dynamics.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-19 DOI: 10.1021/acs.jctc.5c00312

Irene Burghardt

引用次数: 0

Comparative Analysis of Reinforcement Learning Algorithms for Finding Reaction Pathways: Insights from a Large Benchmark Data Set.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-19 DOI: 10.1021/acs.jctc.4c01780

Yoshihiro Matsumura, Koji Tabata, Tamiki Komatsuzaki

{"title":"Comparative Analysis of Reinforcement Learning Algorithms for Finding Reaction Pathways: Insights from a Large Benchmark Data Set.","authors":"Yoshihiro Matsumura, Koji Tabata, Tamiki Komatsuzaki","doi":"10.1021/acs.jctc.4c01780","DOIUrl":"10.1021/acs.jctc.4c01780","url":null,"abstract":"The identification of kinetically feasible reaction pathways that connect a reactant to its product, including numerous intermediates and transition states, is crucial for predicting chemical reactions and elucidating reaction mechanisms. However, as molecular systems become increasingly complex or larger, the number of local minimum structures and transition states grows, which makes this task challenging, even with advanced computational approaches. We introduced a reinforcement learning algorithm to efficiently identify a kinetically feasible reaction pathway between a given local minimum structure for the reactant and a given one for the product, starting from the reactant. The performance of the algorithm was validated using a benchmark data set of large-scale chemical reaction path networks. Several search policies were proposed, using metrics based on energetic or structural similarity to the product's goal structure, for each local minimum structure candidate found during the search. The performances of baseline greedy, random, and uniform search policies varied substantially depending on the system. In contrast, exploration-exploitation balanced policies such as Thompson sampling, probability of improvement, and expected improvement consistently demonstrated stable and high performance. Furthermore, we characterized the search mechanisms that depend on different policies in detail. This study also addressed potential avenues for further research, such as hierarchical reinforcement learning and multiobjective optimization, which could deepen the problem setting explored in this study.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655486","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

Correlated Flat-Bottom Elastic Network Model for Improved Bond Rearrangement in Reaction Paths.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-19 DOI: 10.1021/acs.jctc.4c01549

Shin-Ichi Koda, Shinji Saito

{"title":"Correlated Flat-Bottom Elastic Network Model for Improved Bond Rearrangement in Reaction Paths.","authors":"Shin-Ichi Koda, Shinji Saito","doi":"10.1021/acs.jctc.4c01549","DOIUrl":"https://doi.org/10.1021/acs.jctc.4c01549","url":null,"abstract":"This study introduces correlated flat-bottom elastic network model (CFB-ENM), an extension of our recently developed flat-bottom elastic network model (FB-ENM) for generating plausible reaction paths, i.e., collision-free paths preserving nonreactive parts. While FB-ENM improved upon the widely used image-dependent pair potential (IDPP) by addressing unintended structural distortion and bond breaking, it still struggled with regulating the timing of series of bond breaking and formation. CFB-ENM overcomes this limitation by incorporating structure-based correlation terms. These terms impose constraints on pairs of atom pairs, ensuring immediate formation of new bonds after breaking of existing bonds. Using the direct MaxFlux method, we generated paths for 121 reactions involving main group elements and 35 reactions involving transition metals. We found that CFB-ENM significantly improves reaction paths compared to FB-ENM. CFB-ENM paths exhibited lower maximum DFT energies along the paths in most reactions, with nearly half showing significant energy reductions of several tens of kcal/mol. In the few cases where CFB-ENM yielded higher energy paths, most increases were below 10 kcal/mol. We also confirmed that CFB-ENM reduces computational costs in subsequent precise reaction path or transition state searches compared to FB-ENM. An implementation of CFB-ENM based on the Atomic Simulation Environment is available on GitHub for use in computational chemistry research.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661669","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

Conical Intersections Studied by the Configuration-Interaction-Corrected Tamm-Dancoff Method.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-18 DOI: 10.1021/acs.jctc.4c01768

Lei Xu, Victor M Freixas, Flavia Aleotti, Donald G Truhlar, Sergei Tretiak, Marco Garavelli, Shaul Mukamel, Niranjan Govind

{"title":"Conical Intersections Studied by the Configuration-Interaction-Corrected Tamm-Dancoff Method.","authors":"Lei Xu, Victor M Freixas, Flavia Aleotti, Donald G Truhlar, Sergei Tretiak, Marco Garavelli, Shaul Mukamel, Niranjan Govind","doi":"10.1021/acs.jctc.4c01768","DOIUrl":"https://doi.org/10.1021/acs.jctc.4c01768","url":null,"abstract":"Conical intersections directly mediate the internal energy conversion in photoinduced processes in a wide range of chemical and biological systems. Because of the Brillouin theorem, many conventional electronic structure methods, including configuration interaction with single excitations from a Hartree-Fock reference and time-dependent density functional theory in either the linear response approximation (TDDFT) or Tamm-Dancoff approximation (DFT-TDA), have the wrong dimensionality for conical intersections between the ground state (S0) and the first excited state (S1) of the same multiplicity. This leads to unphysical state crossings. Here, we implement and assess the configuration-interaction-corrected Tamm-Dancoff approximation (CIC-TDA) that restores the correct dimensionality of conical intersections by including the coupling between the reference state and the intersecting excited state. We apply the CIC-TDA method to the S1/S0 conical intersections in ammonia (NH3), ethylene (C2H4), bithiophene (C8H6S2), azobenzene (C12H10N2), and 11-cis retinal protonated Schiff base (PSB11) in vacuo. We show that this black-box approach can produce potential energy surfaces (PESs) of comparable accuracy to multireference wave function methods. The method validated here can allow cost-efficient explorations of photoinduced electronically nonadiabatic dynamics, especially for large molecules and complex systems.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655488","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

Ion Channel Reaction Networks: Dielectric Screening and the Importance of Off-Pathway Flux.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-18 DOI: 10.1021/acs.jctc.4c01569

Hannah Weckel-Dahman, Ryan Carlsen, Alexander Daum, Maxwell He, Tyler G Southam, Jessica M J Swanson

{"title":"Ion Channel Reaction Networks: Dielectric Screening and the Importance of Off-Pathway Flux.","authors":"Hannah Weckel-Dahman, Ryan Carlsen, Alexander Daum, Maxwell He, Tyler G Southam, Jessica M J Swanson","doi":"10.1021/acs.jctc.4c01569","DOIUrl":"https://doi.org/10.1021/acs.jctc.4c01569","url":null,"abstract":"The transport of ions through channels involves multiple rare-event transitions through a web of interconnected intermediates. Extracting open channel mechanisms generally requires quantifying the relative flux through these intermediates in response to a range of electrochemical gradients. Although this is ideally suited to network-based representations like Markov state models (MSMs), the relative contributions from different pathways and the importance of network resolution remain open areas of research. Herein, we use a complementary approach called multiscale responsive kinetic modeling (MsRKM) to explore how the screening of ionic interactions and the competition between multiple mechanistic pathways contribute to channel mechanisms and current profiles of ion channels. We find that explicitly optimizing screened ionic interactions in the MsRKM framework vastly reduces the solution search space, enabling more efficient identification of physically robust solutions. Using a model of the Shaker Kv channel, we demonstrate that even when systems are well described by a single dominant flux pathway, the remaining contributing pathways and off-pathway flux play multiple essential roles, including shifting current profiles and mechanisms in response to different electrochemical gradients. We additionally discover that the current continues to change above the experimentally predicted saturation point. Model systems explain how the degree of dielectric screening influences channel occupancy, the number of contributing pathways, and why current increases or decreases above its experimental saturation point. Our findings emphasize the importance of retaining a full network description to identify and understand ion channel mechanisms.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655498","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

Can Coarse-Grained Molecular Dynamics Simulations Predict Pharmaceutical Crystal Growth?

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-17 DOI: 10.1021/acs.jctc.5c00040

Linghao Shi, Futianyi Wang, Taraknath Mandal, Ronald G Larson

{"title":"Can Coarse-Grained Molecular Dynamics Simulations Predict Pharmaceutical Crystal Growth?","authors":"Linghao Shi, Futianyi Wang, Taraknath Mandal, Ronald G Larson","doi":"10.1021/acs.jctc.5c00040","DOIUrl":"https://doi.org/10.1021/acs.jctc.5c00040","url":null,"abstract":"To investigate the ability of coarse-grained molecular dynamics simulations to predict the relative growth rates of crystal facets of pharmaceutical molecules, we apply two coarse-graining strategies to two drug molecules, phenytoin and carbamazepine. In the first method, we map an atomistic model to a MARTINI-level coarse-grained (CG) force field that uses 2 or 3 heavy atoms per bead. This is followed by applying Particle Swarm Optimization (PSO), a global optimum searching algorithm, to the CG Lennard-Jones intermolecular potentials to fit the radial distribution functions of both the crystalline and melt structures. In the second, a coarser-grained method, we map 5 or more heavy atoms into one bead with the help of the Iterative Boltzmann Inversion (IBI) method to derive a tabulated longer-range force field (FF). Simulations using the FF's derived from both strategies were able to stabilize the crystal in the correct structure and to predict crystal growth from the melt with modest computational resources. We evaluate the advantages and limitations of both methods and compare the relative growth rates of various facets of both drug crystals with those predicted by the Bravais-Friedel-Donnay-Harker (BFDH) and attachment energy (AE) theories. While all methods, except for the simulations conducted with the coarser-grained IBI-generated model, produced similarly good results for phenytoin, the finer-grained PSO-generated FF using MARTINI mapping rules outperformed the other methods in its prediction of the facet growth rates and resulting crystalline morphology for carbamazepine.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646413","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

Coarse-Grained Modeling of a Metal–Organic Framework/Polymer Composite and Its Gas Adsorption at the Nanoparticle Level

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-17 DOI: 10.1021/acs.jctc.4c0134110.1021/acs.jctc.4c01341

Cecilia M. S. Alvares, and , Rocio Semino*,

{"title":"Coarse-Grained Modeling of a Metal–Organic Framework/Polymer Composite and Its Gas Adsorption at the Nanoparticle Level","authors":"Cecilia M. S. Alvares,  and , Rocio Semino*, ","doi":"10.1021/acs.jctc.4c0134110.1021/acs.jctc.4c01341","DOIUrl":"https://doi.org/10.1021/acs.jctc.4c01341https://doi.org/10.1021/acs.jctc.4c01341","url":null,"abstract":"Simulations have acted as a cornerstone to understand the MOF/polymer interface structure; however, no molecular-level simulation has yet been performed at the nanoparticle scale. In this work, a hybrid MARTINI/force matching (FM) force field was developed and successfully implemented to model the ZIF-8/PVDF composite at a coarse-grained resolution. Interphase interactions were modeled using FM potentials, which strive to reasonably reproduce the forces from an atomistic benchmark model, while intraphase interactions were modeled using the general-purpose MARTINI potentials. Systems made of a ZIF-8 nanoparticle embedded into a PVDF matrix were considered to evaluate the effect of nanoparticle size and morphology in the polymer structuration and in the CO2 adsorption. Results show that simulations at the nanoparticle level are crucial for depicting polymer penetration. Notably, the smallest nanoparticle exhibited the least extent of polymer penetration, while the cubic nanoparticle exhibited the highest amount. Polymer conformation and local density values change following the same trend in all ZIF-8/PVDF systems depending on whether the polymer lies inside or outside the nanoparticle domain. All composite models present more significant CO2 adsorption in the nanoparticle domain than in the PVDF phase, in agreement with experiments. More remarkably, the small rhombic dodecahedron ZIF-8/PVDF system presents a larger equilibrium amount of gas adsorbed at ambient conditions compared to the other two systems, in alignment with the observed polymer penetration trend. On the other hand, comparison of CO2 adsorption capacities in cubic and rhombic dodecahedron ZIF-8 nanoparticles of similar sizes reveals that the former is more advantageous for CO2 adsorption.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"21 6","pages":"3142–3155 3142–3155"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143678682","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

A Theoretical Model for Linear and Nonlinear Spectroscopy of Plexcitons.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-17 DOI: 10.1021/acs.jctc.5c00048

Chenghong Huang, Shuming Bai, Qiang Shi

{"title":"A Theoretical Model for Linear and Nonlinear Spectroscopy of Plexcitons.","authors":"Chenghong Huang, Shuming Bai, Qiang Shi","doi":"10.1021/acs.jctc.5c00048","DOIUrl":"https://doi.org/10.1021/acs.jctc.5c00048","url":null,"abstract":"We present a theoretical model to investigate the dynamics and spectroscopic properties of a plexciton system consisting of a molecular exciton coupled to a single short-lived plasmonic mode. The exciton is described as a two-level system (TLS), while the plasmonic mode is treated as a dissipative harmonic oscillator. The hierarchical equations of motion method is employed to simulate energy transfer dynamics, absorption spectra, and two-dimensional electronic spectra (2DES) of the system across a range of coupling strengths. It is shown that increasing the exciton-plasmon coupling strength drives a transition in the absorption spectra from an asymmetric Fano line shape to a Rabi splitting pattern, while coupling the TLS to intramolecular vibrational modes reduces the central dip of the absorption spectra and makes the line shape more symmetric. The simulated 2DES exhibit distinct features compared to those of a coupled molecular dimer, highlighting the unique nonlinear response of plexciton systems. In addition, a \"breathing mode\" pattern observed in the strong coupling regime can serve as a direct evidence of Rabi oscillation.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646407","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 TPS Shooting Using Computer Vision to Generate Ensemble of Trajectories.

IF 5.7 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-03-17 DOI: 10.1021/acs.jctc.4c01725

Kseniia Korchagina, Steven D Schwartz

引用次数: 0