Abstract The pseudomode framework provides an efficient description of open quantum systems in non-Markovian and nonperturbative coupling regimes by utilizing simple Markovian Lindblad master equations that incorporate a set of damped bosonic pseudomodes. Developing an efficient numerical scheme to solve these equations accurately is highly desirable. In this work, we propose a modified multiple Davydov D1 density operator ansatz and combine it with the Dirac–Frenkel time-dependent variational principle to simulate the dynamics governed by these master equations. We apply this variational method to the spin-boson model, both with and without a periodic external driving field, and compute both single- and two-time expectation values in non-Markovian, strong-coupling regimes. The accuracy of our variational approach is validated by comparing its predictions with results obtained from the small matrix path integral method. We demonstrate that the variational and path-integral approaches are in excellent agreement for both single- and two-time expectations across nondriven and driven cases, spanning both low- and high-temperature regimes. Our results establish the reliability and broad applicability of the pseudomode-based variational approach for calculating two-time correlation functions in open quantum systems.
{"title":"Accurate Two-Time\u0000Correlation from a Pseudomode-Based\u0000Variational Approach with the Multiple Davydov D1 Density\u0000Operator","authors":"Yiying Yan,Zhiguo Lü,Yuguo Su,JunYan Luo,Yang Zhao","doi":"10.1021/acs.jctc.6c01283","DOIUrl":"https://doi.org/10.1021/acs.jctc.6c01283","url":null,"abstract":"Abstract The pseudomode framework provides an efficient description of open quantum systems in non-Markovian and nonperturbative coupling regimes by utilizing simple Markovian Lindblad master equations that incorporate a set of damped bosonic pseudomodes. Developing an efficient numerical scheme to solve these equations accurately is highly desirable. In this work, we propose a modified multiple Davydov D1 density operator ansatz and combine it with the Dirac–Frenkel time-dependent variational principle to simulate the dynamics governed by these master equations. We apply this variational method to the spin-boson model, both with and without a periodic external driving field, and compute both single- and two-time expectation values in non-Markovian, strong-coupling regimes. The accuracy of our variational approach is validated by comparing its predictions with results obtained from the small matrix path integral method. We demonstrate that the variational and path-integral approaches are in excellent agreement for both single- and two-time expectations across nondriven and driven cases, spanning both low- and high-temperature regimes. Our results establish the reliability and broad applicability of the pseudomode-based variational approach for calculating two-time correlation functions in open quantum systems.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"160 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209800","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}
Pub Date : 2026-10-16DOI: 10.1021/acs.jctc.6c01550
Sayan Bhowmik,Andrew J. Medford,Phanish Suryanarayana
Abstract We present a bulk boundary condition formalism for semi-infinite surfaces in Kohn–Sham density functional theory. The approach exploits the nearsightedness of electronic interactions to confine the calculation to a localized surface region, where the electron density is evaluated via density matrix decay with bulk values of potential imposed in the interior, and the electrostatic potential is solved subject to bulk boundary conditions. We demonstrate the accuracy and efficiency of the formalism through representative calculations.
{"title":"Bulk Boundary Condition\u0000for Semi-Infinite Surfaces\u0000in Density Functional Theory","authors":"Sayan Bhowmik,Andrew J. Medford,Phanish Suryanarayana","doi":"10.1021/acs.jctc.6c01550","DOIUrl":"https://doi.org/10.1021/acs.jctc.6c01550","url":null,"abstract":"Abstract We present a bulk boundary condition formalism for semi-infinite surfaces in Kohn–Sham density functional theory. The approach exploits the nearsightedness of electronic interactions to confine the calculation to a localized surface region, where the electron density is evaluated via density matrix decay with bulk values of potential imposed in the interior, and the electrostatic potential is solved subject to bulk boundary conditions. We demonstrate the accuracy and efficiency of the formalism through representative calculations.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"13 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209801","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}
Pub Date : 2026-10-16DOI: 10.1021/acs.jctc.6c01341
Tao Wang,Tianying Yan
Abstract Highly concentrated electrolytes (HCEs) have attracted considerable attention for lithium batteries owing to their wide electrochemical stability windows and favorable interfacial properties, which originate from their anion-rich solvation structures. The dynamics of lithium ions play a key role for HCEs performance; however, a clear mechanistic understanding of lithium-ion (Li+) transport within percolating ionic networks of HCEs remains elusive. Here, we performed a molecular dynamics simulation on a lithium bis(fluorosulfonyl)imide/1,2-dimethoxyethane (LiFSI/DME) HCE system and then constructed a Markov state model (MSM) using a graph convolutional neural network architecture named GDyNet to investigate the dynamics of lithium ions. The MSM classifies lithium ions into three distinct metastable states based on their local coordination environments: nonsolvated state (State 0), moderately solvated state (State 1), and highly solvated state (State 2), which are kinetically well separated and exhibit distinct dynamic behaviors. Li+ transport in LiFSI/DME HCE is dominated by the self-transitions within each state rather than interstate transitions. During the slow interconversion among the three metastable states, FSI– anions in the coordination shells undergo frequent exchange. The moderately solvated state exhibits the fastest diffusion, followed by the highly solvated state, and the nonsolvated state exhibits the slowest. By integrating the Green–Kubo relation and MSMs, we quantified the relative contributions of these state transitions to Li+ conduction. The transitions from the nonsolvated state contribute negligibly to Li+ conduction, and the dominant contributions originate from the moderately and highly solvated states. The insights obtained from the MSM provide an in-depth mechanistic understanding of Li+ dynamics in HCEs.
{"title":"Elucidating Lithium-Ion\u0000Dynamics in Highly Concentrated\u0000Electrolytes with Markov State Models","authors":"Tao Wang,Tianying Yan","doi":"10.1021/acs.jctc.6c01341","DOIUrl":"https://doi.org/10.1021/acs.jctc.6c01341","url":null,"abstract":"Abstract Highly concentrated electrolytes (HCEs) have attracted considerable attention for lithium batteries owing to their wide electrochemical stability windows and favorable interfacial properties, which originate from their anion-rich solvation structures. The dynamics of lithium ions play a key role for HCEs performance; however, a clear mechanistic understanding of lithium-ion (Li+) transport within percolating ionic networks of HCEs remains elusive. Here, we performed a molecular dynamics simulation on a lithium bis(fluorosulfonyl)imide/1,2-dimethoxyethane (LiFSI/DME) HCE system and then constructed a Markov state model (MSM) using a graph convolutional neural network architecture named GDyNet to investigate the dynamics of lithium ions. The MSM classifies lithium ions into three distinct metastable states based on their local coordination environments: nonsolvated state (State 0), moderately solvated state (State 1), and highly solvated state (State 2), which are kinetically well separated and exhibit distinct dynamic behaviors. Li+ transport in LiFSI/DME HCE is dominated by the self-transitions within each state rather than interstate transitions. During the slow interconversion among the three metastable states, FSI– anions in the coordination shells undergo frequent exchange. The moderately solvated state exhibits the fastest diffusion, followed by the highly solvated state, and the nonsolvated state exhibits the slowest. By integrating the Green–Kubo relation and MSMs, we quantified the relative contributions of these state transitions to Li+ conduction. The transitions from the nonsolvated state contribute negligibly to Li+ conduction, and the dominant contributions originate from the moderately and highly solvated states. The insights obtained from the MSM provide an in-depth mechanistic understanding of Li+ dynamics in HCEs.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"12 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210476","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}
Pub Date : 2026-10-16DOI: 10.1021/acs.jctc.6c01448
Joonmyung Choi
Abstract Finite-temperature velocity autocorrelation functions (VACFs) provide a direct connection between molecular dynamics trajectories and vibrational, anharmonic, and relaxation behavior, but their reliable evaluation can require substantial atomistic sampling. In this study, a physics-constrained reduced operator is developed from short stationary molecular dynamics trajectories. The formulation combines a temperature-specific quasiharmonic eigenspectrum with compact corrections for finite-temperature frequency shifts and the loss of modal coherence. A finite-memory extension preserves the equilibrium symmetry and short-time consistency of the correlation function without altering the identified long-time behavior. The method was validated using blind trajectories, repeated data partitions, bootstrap analysis, and independent spectral calculations. For crystalline Si over 300–700 K, the reduced operator reproduces the finite-temperature VACF with an error comparable to the variability among independent molecular dynamics realizations, while retaining physically interpretable spectral trends. The same operator hierarchy can be reidentified for the tested monatomic crystalline systems described by Tersoff, Stillinger-Weber, and embedded-atom potentials. Within this demonstrated scope, the framework converts short atomistic trajectories into a directly evaluable representation of finite-temperature correlation dynamics, providing a practical molecular simulation route for reconstructing VACFs across temperatures and interaction models.
{"title":"Reconstructing\u0000Finite-Temperature Velocity Autocorrelation\u0000Functions from Short Molecular Dynamics Trajectories","authors":"Joonmyung Choi","doi":"10.1021/acs.jctc.6c01448","DOIUrl":"https://doi.org/10.1021/acs.jctc.6c01448","url":null,"abstract":"Abstract Finite-temperature velocity autocorrelation functions (VACFs) provide a direct connection between molecular dynamics trajectories and vibrational, anharmonic, and relaxation behavior, but their reliable evaluation can require substantial atomistic sampling. In this study, a physics-constrained reduced operator is developed from short stationary molecular dynamics trajectories. The formulation combines a temperature-specific quasiharmonic eigenspectrum with compact corrections for finite-temperature frequency shifts and the loss of modal coherence. A finite-memory extension preserves the equilibrium symmetry and short-time consistency of the correlation function without altering the identified long-time behavior. The method was validated using blind trajectories, repeated data partitions, bootstrap analysis, and independent spectral calculations. For crystalline Si over 300–700 K, the reduced operator reproduces the finite-temperature VACF with an error comparable to the variability among independent molecular dynamics realizations, while retaining physically interpretable spectral trends. The same operator hierarchy can be reidentified for the tested monatomic crystalline systems described by Tersoff, Stillinger-Weber, and embedded-atom potentials. Within this demonstrated scope, the framework converts short atomistic trajectories into a directly evaluable representation of finite-temperature correlation dynamics, providing a practical molecular simulation route for reconstructing VACFs across temperatures and interaction models.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"89 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210477","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}
Pub Date : 2026-10-15DOI: 10.1021/acs.jctc.6c01471
P. Maiz-Pastor,E. Brémond,A. J. Pérez-Jiménez,C. Adamo,J. C. Sancho-García
Abstract We extend the restored-regularized Strongly Constrained and Appropriately Normed (r2SCAN) nonempirical exchange-correlation functional to the Range-Separation eXchange (RSX) scheme, RSX-r2SCAN, where the range-separation parameter (ω) is obtained by applying a first-principles constraint, thus not relying on any empirical fitting. The corresponding exchange-correlation hybrid (i.e., RSX-r2SCAN0) and double-hybrid (i.e., RSX-r2SCAN-QIDH) versions are also built following this procedure, concomitantly assessing all the models on relevant systems (e.g., increasingly larger clusters of noninteracting He atoms) and a large data set of ionization potentials (e.g., GW100). The assessment is also done using the GMTKN55 database for general main-group thermochemistry, kinetics, and noncovalent interactions, along with the WTMAD-2 error metric and a more recent one called WTMAD-4. The assessment is completed with a detailed analysis of some of the GMTKN55 subsets most affected by self-interaction errors. Finally, the models are coupled to the VV10 correlation energy functional (RSX-r2SCAN-NL, r2SCAN0-NL, and RSX-r2SCAN-QIDH-NL) for nonlocal and long-range electronic effects, to accurately address noncovalently bound systems as well.
{"title":"A New Family of\u0000Nonempirical Range-Separated Functionals:\u0000RSX-r2SCAN, RSX-r2SCAN0, and RSX-r2SCAN-QIDH","authors":"P. Maiz-Pastor,E. Brémond,A. J. Pérez-Jiménez,C. Adamo,J. C. Sancho-García","doi":"10.1021/acs.jctc.6c01471","DOIUrl":"https://doi.org/10.1021/acs.jctc.6c01471","url":null,"abstract":"Abstract We extend the restored-regularized Strongly Constrained and Appropriately Normed (r2SCAN) nonempirical exchange-correlation functional to the Range-Separation eXchange (RSX) scheme, RSX-r2SCAN, where the range-separation parameter (ω) is obtained by applying a first-principles constraint, thus not relying on any empirical fitting. The corresponding exchange-correlation hybrid (i.e., RSX-r2SCAN0) and double-hybrid (i.e., RSX-r2SCAN-QIDH) versions are also built following this procedure, concomitantly assessing all the models on relevant systems (e.g., increasingly larger clusters of noninteracting He atoms) and a large data set of ionization potentials (e.g., GW100). The assessment is also done using the GMTKN55 database for general main-group thermochemistry, kinetics, and noncovalent interactions, along with the WTMAD-2 error metric and a more recent one called WTMAD-4. The assessment is completed with a detailed analysis of some of the GMTKN55 subsets most affected by self-interaction errors. Finally, the models are coupled to the VV10 correlation energy functional (RSX-r2SCAN-NL, r2SCAN0-NL, and RSX-r2SCAN-QIDH-NL) for nonlocal and long-range electronic effects, to accurately address noncovalently bound systems as well.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"64 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209802","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}
Pub Date : 2026-10-15DOI: 10.1021/acs.jctc.6c01815
Xuan Peng
Abstract Reaction ensemble Monte Carlo samples chemical composition directly but usually treats the explicit environment with classical nuclei, whereas path-integral methods represent nuclear quantum effects explicitly but generally infer reaction equilibria from partition-function or free-energy ratios between predefined states. We formulate path-integral reaction ensemble Monte Carlo (PI-RxMC), a reaction-constrained expanded ensemble that samples chemical sectors and nuclear paths jointly, and derive the Metropolis-Hastings rule for sector changes, including sector weights, normalization factors, proposal probabilities, coordinate transformations, and Jacobians; for fixed nuclei with changing bonding topology, the free-ring-polymer contribution cancels exactly. Independent finite-P analytical, bond-topology, and rovibrational benchmarks validate the method, and direct sector-population estimates for H2 + D2 ⇌ 2HD agree with independent quantum results from 200 to 700 K. A second benchmark, AB ⇌ A + B with Δν = +1, explicitly recovers the reaction-volume and 1 M standard-state factors and exhibits a nearly 3-fold nuclear-quantum enhancement of the equilibrium constant. A bead-level slit field further demonstrates coupling to an explicit environment.
反应系综蒙特卡罗方法直接对化学组成进行采样，但通常用经典原子核处理显式环境，而路径积分方法明确地表示核量子效应，但通常从预定义状态之间的配分函数或自由能比推断反应平衡。我们制定了路径积分反应系系蒙特卡罗（PI-RxMC），这是一个反应约束的扩展系系，可以联合采样化学区域和核路径，并推导了区域变化的Metropolis-Hastings规则，包括区域权重、归一化因子、建议概率、坐标变换和雅可比；对于改变成键拓扑的固定原子核，自由环聚合物的贡献完全抵消。独立的有限p分析，键拓扑和旋转振动基准验证了该方法，H2 + D2 + 2HD的直接扇形种群估计与200至700 K的独立量子结果一致。第二个基准AB + A + B （Δν = +1）明确恢复了反应体积和1 M标准态因子，并显示出平衡常数近3倍的核量子增强。头级狭缝场进一步展示了与显式环境的耦合。
{"title":"Direct Sampling\u0000of Nuclear-Quantum Chemical Equilibria\u0000by Path-Integral Reaction Ensemble Monte Carlo","authors":"Xuan Peng","doi":"10.1021/acs.jctc.6c01815","DOIUrl":"https://doi.org/10.1021/acs.jctc.6c01815","url":null,"abstract":"Abstract Reaction ensemble Monte Carlo samples chemical composition directly but usually treats the explicit environment with classical nuclei, whereas path-integral methods represent nuclear quantum effects explicitly but generally infer reaction equilibria from partition-function or free-energy ratios between predefined states. We formulate path-integral reaction ensemble Monte Carlo (PI-RxMC), a reaction-constrained expanded ensemble that samples chemical sectors and nuclear paths jointly, and derive the Metropolis-Hastings rule for sector changes, including sector weights, normalization factors, proposal probabilities, coordinate transformations, and Jacobians; for fixed nuclei with changing bonding topology, the free-ring-polymer contribution cancels exactly. Independent finite-P analytical, bond-topology, and rovibrational benchmarks validate the method, and direct sector-population estimates for H2 + D2 ⇌ 2HD agree with independent quantum results from 200 to 700 K. A second benchmark, AB ⇌ A + B with Δν = +1, explicitly recovers the reaction-volume and 1 M standard-state factors and exhibits a nearly 3-fold nuclear-quantum enhancement of the equilibrium constant. A bead-level slit field further demonstrates coupling to an explicit environment.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"482 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209803","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}
Pub Date : 2026-10-14DOI: 10.1021/acs.jctc.6c00811
Gabriele Amante,Giuseppe Cassone
Abstract The catalytic properties of water microdroplets are often attributed to strong interfacial electric fields, yet the nature of these fields remains debated. Here we combine quantum data-driven many-body molecular dynamics, ab initio resampling, and spatially resolved electric field evaluations to rigorously assess intermolecular electrostatics at the flat air–water interface. The calculated local intermolecular quantity may be viewed as a microsolvation electric-field descriptor of the environment experienced by a molecular species approaching or residing near the interface. By classifying molecules using two complementary interface definitions and going beyond classical partial-charge methods, we obtain field maps directly from the electronic charge density. Similarly to recent experimental findings, the bulk and interfacial field distributions overlap strongly, while their mean values exhibit a modest interfacial reduction of ∼10%. Correlations with the density profiles obtained from different reference frames indicate that density depletion near the surface contributes to this attenuation. Beyond offering an electron-density-based methodology for evaluating local electric fields, these findings suggest that exceptionally strong local fields alone may not fully account for the enhanced reactivity reported in microdroplets.
{"title":"Why Interfacial\u0000Electric Fields May Appear Weaker:\u0000An Electron-Density-Based Study of the Flat Air–Water Interface","authors":"Gabriele Amante,Giuseppe Cassone","doi":"10.1021/acs.jctc.6c00811","DOIUrl":"https://doi.org/10.1021/acs.jctc.6c00811","url":null,"abstract":"Abstract The catalytic properties of water microdroplets are often attributed to strong interfacial electric fields, yet the nature of these fields remains debated. Here we combine quantum data-driven many-body molecular dynamics, ab initio resampling, and spatially resolved electric field evaluations to rigorously assess intermolecular electrostatics at the flat air–water interface. The calculated local intermolecular quantity may be viewed as a microsolvation electric-field descriptor of the environment experienced by a molecular species approaching or residing near the interface. By classifying molecules using two complementary interface definitions and going beyond classical partial-charge methods, we obtain field maps directly from the electronic charge density. Similarly to recent experimental findings, the bulk and interfacial field distributions overlap strongly, while their mean values exhibit a modest interfacial reduction of ∼10%. Correlations with the density profiles obtained from different reference frames indicate that density depletion near the surface contributes to this attenuation. Beyond offering an electron-density-based methodology for evaluating local electric fields, these findings suggest that exceptionally strong local fields alone may not fully account for the enhanced reactivity reported in microdroplets.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"14 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210478","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}
Abstract The three human YTH-domain family proteins (YTHDF1, YTHDF2, and YTHDF3) are highly homologous and recognize the N6-methyladenosine (m6A) modification of mRNA with essentially identical binding modes and affinities. This homogeneity challenges the well-established view that different YTHDF proteins play distinct cellular functions (the specificity view), with an emerging argument that these proteins may instead play redundant roles. To study this apparent discrepancy, we investigated the mechanism of binding of m6A-containing RNA using mutagenesis, X-ray crystallography, isothermal titration calorimetry (ITC), and molecular dynamics simulations. Specifically, we compared different properties of YTHDF proteins, including their binding capacities to m6A-RNA, conformational changes, and homodimerization propensity. Our results show that the YTHDF proteins share an identical binding mode of m6A-RNA, which requires rare protonation of m6A for binding. Additionally, the three proteins share a similar open-closed switch for their recognition loop regulating the m6A binding. On the other hand, ITC data and crystal structures provide consistent evidence that the YTHDF proteins differ significantly in the flexibility of the recognition loop and its conformational preferences. Only YTHDF1 can homodimerize, which prevents binding to m6A-RNA. Furthermore, we integrate the available biophysical and biochemical evidence to define both the shared and distinct features of YTHDF1–3 in m6A-RNA recognition and propose a hybrid model that reconciles the redundancy-specificity debate. Finally, we discuss the limitations of the work and propose experiments for validating the presented model.
{"title":"Recognition Loop\u0000Dynamics Differentiates m6A-mRNA Reader Domains\u0000of YTHDF Proteins","authors":"Yaozong Li,Rajiv Kumar Bedi,Pedro Ojeda-May,Amedeo Caflisch","doi":"10.1021/acs.jctc.6c01247","DOIUrl":"https://doi.org/10.1021/acs.jctc.6c01247","url":null,"abstract":"Abstract The three human YTH-domain family proteins (YTHDF1, YTHDF2, and YTHDF3) are highly homologous and recognize the N6-methyladenosine (m6A) modification of mRNA with essentially identical binding modes and affinities. This homogeneity challenges the well-established view that different YTHDF proteins play distinct cellular functions (the specificity view), with an emerging argument that these proteins may instead play redundant roles. To study this apparent discrepancy, we investigated the mechanism of binding of m6A-containing RNA using mutagenesis, X-ray crystallography, isothermal titration calorimetry (ITC), and molecular dynamics simulations. Specifically, we compared different properties of YTHDF proteins, including their binding capacities to m6A-RNA, conformational changes, and homodimerization propensity. Our results show that the YTHDF proteins share an identical binding mode of m6A-RNA, which requires rare protonation of m6A for binding. Additionally, the three proteins share a similar open-closed switch for their recognition loop regulating the m6A binding. On the other hand, ITC data and crystal structures provide consistent evidence that the YTHDF proteins differ significantly in the flexibility of the recognition loop and its conformational preferences. Only YTHDF1 can homodimerize, which prevents binding to m6A-RNA. Furthermore, we integrate the available biophysical and biochemical evidence to define both the shared and distinct features of YTHDF1–3 in m6A-RNA recognition and propose a hybrid model that reconciles the redundancy-specificity debate. Finally, we discuss the limitations of the work and propose experiments for validating the presented model.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"220 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210228","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}
Abstract Through spin-selective intersystem crossings (ISCs) among photoexcited electronic states, organic π-diradicals can be spin-polarized by optical excitation, positioning them as long-lived, tunable, and scalable qubits. Recent advancements have utilized triplet π-carbenes of bent structures, which unlock an additional spin-selective ISC channel between the ground states, improving the qubit’s spin–optical properties. However, bent π-carbenes also lose spin selectivity in the excited-state ISC step and a compromise has yet to be found. In this work, we balance the two effects by developing a minimal Hamiltonian for bent π-carbenes, the first of its kind, and solving its spin–optical interactions analytically. Our approach is a valuable alternative to large-scale ab initio screenings, which are highly intensive given the costs of existing open-shell ab initio methods. We find the ideal π-carbene to have a high spin density on its central atom and excitations dominated by HOMO-to-SOMO transitions. These strategies minimize deleterious ISC steps through destructive interferences, which can be accentuated by populating the carbene nonbonding orbital. These chemically intuitive results not only inform qubit designs but also offer a minimal Hamiltonian framework for accelerating high-throughput discovery of optically addressable π-carbenes. As an illustration, we exemplified our design rules on a realistic molecular prototype, completed by a rigorous ab initio characterization over different carbene bond angles.
{"title":"Quantifying the\u0000Spin–Optical Properties of\u0000Bent π-Carbene Molecular Qubits","authors":"Yong Rui Poh,Xiao Chen,Hai-Ping Cheng,Joel Yuen-Zhou","doi":"10.1021/acs.jctc.6c01277","DOIUrl":"https://doi.org/10.1021/acs.jctc.6c01277","url":null,"abstract":"Abstract Through spin-selective intersystem crossings (ISCs) among photoexcited electronic states, organic π-diradicals can be spin-polarized by optical excitation, positioning them as long-lived, tunable, and scalable qubits. Recent advancements have utilized triplet π-carbenes of bent structures, which unlock an additional spin-selective ISC channel between the ground states, improving the qubit’s spin–optical properties. However, bent π-carbenes also lose spin selectivity in the excited-state ISC step and a compromise has yet to be found. In this work, we balance the two effects by developing a minimal Hamiltonian for bent π-carbenes, the first of its kind, and solving its spin–optical interactions analytically. Our approach is a valuable alternative to large-scale ab initio screenings, which are highly intensive given the costs of existing open-shell ab initio methods. We find the ideal π-carbene to have a high spin density on its central atom and excitations dominated by HOMO-to-SOMO transitions. These strategies minimize deleterious ISC steps through destructive interferences, which can be accentuated by populating the carbene nonbonding orbital. These chemically intuitive results not only inform qubit designs but also offer a minimal Hamiltonian framework for accelerating high-throughput discovery of optically addressable π-carbenes. As an illustration, we exemplified our design rules on a realistic molecular prototype, completed by a rigorous ab initio characterization over different carbene bond angles.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"14 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209804","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}
Abstract Nonradiative decay in photoexcited molecular systems is driven by nuclear motion toward conical intersections (CIs), where electronic states become degenerate and nonadiabatic transitions occur. Identifying the nuclear degrees of freedom responsible for CI access from nonadiabatic molecular dynamics (NAMD) simulations remains challenging, because the underlying motions are high-dimensional and collective. Here, we introduce an unsupervised, information-theoretic framework based on differentiable information imbalance (DII) to identify the nuclear coordinates governing CI access directly from trajectory surface hopping (TSH) simulations. By quantifying correlations between structural descriptors and electronic observables, including energy gaps and oscillator strengths, the method ranks nuclear degrees of freedom by their predictive relevance. A multistep protocol then extracts low-dimensional, physically interpretable modes associated with nonradiative decay. We apply the framework to the methaniminium cation, furan, l-glutamine, l-pyroglutamine ammonium, and a photoactive molecular motor. Across all systems, the method recovers known mechanistic coordinates while revealing the relative importance of competing modes when multiple structural distortions contribute to the CI access. The analysis also reveals a systematic distinction between observables: energy gaps are typically governed by a small number of localized coordinates, whereas oscillator strengths depend on more-extended and distributed structural rearrangements. Overall, the DII-based framework combines predictive power with direct interpretability, providing a general and scalable route for extracting mechanistic insights from high-dimensional NAMD data and constructing reduced-dimensional models of excited-state dynamics.
{"title":"Machine Learning the Nonradiative Decay Modes in Photochemical\u0000Processes","authors":"Debarshi Banerjee,Gonzalo Díaz Mirón,Alex Rodriguez,Ali Hassanali","doi":"10.1021/acs.jctc.6c00940","DOIUrl":"https://doi.org/10.1021/acs.jctc.6c00940","url":null,"abstract":"Abstract Nonradiative decay in photoexcited molecular systems is driven by nuclear motion toward conical intersections (CIs), where electronic states become degenerate and nonadiabatic transitions occur. Identifying the nuclear degrees of freedom responsible for CI access from nonadiabatic molecular dynamics (NAMD) simulations remains challenging, because the underlying motions are high-dimensional and collective. Here, we introduce an unsupervised, information-theoretic framework based on differentiable information imbalance (DII) to identify the nuclear coordinates governing CI access directly from trajectory surface hopping (TSH) simulations. By quantifying correlations between structural descriptors and electronic observables, including energy gaps and oscillator strengths, the method ranks nuclear degrees of freedom by their predictive relevance. A multistep protocol then extracts low-dimensional, physically interpretable modes associated with nonradiative decay. We apply the framework to the methaniminium cation, furan, l-glutamine, l-pyroglutamine ammonium, and a photoactive molecular motor. Across all systems, the method recovers known mechanistic coordinates while revealing the relative importance of competing modes when multiple structural distortions contribute to the CI access. The analysis also reveals a systematic distinction between observables: energy gaps are typically governed by a small number of localized coordinates, whereas oscillator strengths depend on more-extended and distributed structural rearrangements. Overall, the DII-based framework combines predictive power with direct interpretability, providing a general and scalable route for extracting mechanistic insights from high-dimensional NAMD data and constructing reduced-dimensional models of excited-state dynamics.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"112 3 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210230","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：