Journal of Chemical Theory and Computation最新文献

Sequence-Dependent Conformational Landscapes of Intrinsically Disordered Proteins Reveal Asymmetric Chain Compaction. 序列依赖的内在无序蛋白质的构象景观揭示了不对称链压实。

IF 5.5 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-10-25 DOI: 10.1021/acs.jctc.5c01329

Cong Wang,Bin Zhang

{"title":"Sequence-Dependent Conformational Landscapes of Intrinsically Disordered Proteins Reveal Asymmetric Chain Compaction.","authors":"Cong Wang,Bin Zhang","doi":"10.1021/acs.jctc.5c01329","DOIUrl":"https://doi.org/10.1021/acs.jctc.5c01329","url":null,"abstract":"Intrinsically disordered proteins (IDPs) exhibit highly dynamic and heterogeneous conformational ensembles that are strongly influenced by sequence features. While global properties such as chain compaction and scaling behavior have been widely studied, they often fail to resolve the fine-grained, sequence-specific structural variation that underlies IDP function. Here, we perform long-time scale atomistic simulations of 47 representative IDP sequences from the yeast proteome to systematically investigate the relationship between sequence composition and conformational ensemble. To analyze the high-dimensional structural data, we apply uniform manifold approximation and projection (UMAP), a nonlinear dimensionality reduction technique that preserves local structural relationships. The resulting low-dimensional embeddings effectively differentiate IDP ensembles and reveal a novel descriptor─local compactness asymmetry─that quantifies directional differences in chain organization. This metric, denoted γRg, captures conformational features orthogonal to traditional global measures such as radius of gyration and end-to-end distance. We show that γRg correlates with sequence-level asymmetries in charge and hydropathy, and that conformational dynamics preferentially occur in the more extended region of the chain. The simulation data set generated in this work also provides a valuable resource for training machine learning models and developing improved coarse-grained force fields for disordered proteins.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"49 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357775","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

Ensemble-Based Precision Refinement of All-Atom Nucleic Acid Force Fields Guided by NMR NOE Pair-Distance Measurements. 基于核磁共振NOE对距离测量的全原子核酸力场集成精确细化。

IF 5.5 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-10-24 DOI: 10.1021/acs.jctc.5c01075

Hyeonjun Kim,Youngshang Pak

引用次数: 0

A Scoring Function for Monolayer-Protected Gold Nanoparticles Capable of Recognizing Small Organic Molecules in Solution. 一种能识别溶液中有机小分子的单层保护金纳米颗粒评分函数。

IF 5.5 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-10-24 DOI: 10.1021/acs.jctc.5c01278

Joseph Wallace,Laura Riccardi,Fabrizio Mancin,Marco De Vivo

{"title":"A Scoring Function for Monolayer-Protected Gold Nanoparticles Capable of Recognizing Small Organic Molecules in Solution.","authors":"Joseph Wallace,Laura Riccardi,Fabrizio Mancin,Marco De Vivo","doi":"10.1021/acs.jctc.5c01278","DOIUrl":"https://doi.org/10.1021/acs.jctc.5c01278","url":null,"abstract":"Ligand-coated gold nanoparticles (AuNPs) can act as self-organized nanoreceptors capable of selectively recognizing small organic molecules (analytes) in solution. This ability can be applied in several fields, with NMR chemosensing being a notable example. To advance the rational design of such AuNP-based nanosensors, we present a data-driven scoring function to rapidly estimate AuNP-analyte binding affinities, thus allowing fast in silico prescreening of ligand-coated AuNP sensors. This scoring function implements chemical similarity, hydrophobicity, and charge complementarity as key molecular descriptors, demonstrating excellent predictive accuracy when validated against experimental data (R2 = 0.85, MAE = 0.45 kcal/mol). Enhanced sampling molecular dynamics on representative systems revealed that ligand flexibility, monolayer packing, and hydrogen bonding critically shape binding interactions, particularly for weak binding systems. Together, these data-driven and atomistic insights offer a robust framework for the rational design and optimization of AuNP-based nanosensors.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"19 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351466","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

Mixed Quantum/Classical Theory for Rotational Excitation of HDO in Collisions with H2: Symmetry Breaking Effects and Time-Dependent Dynamics. HDO与H2碰撞中旋转激发的混合量子/经典理论：对称破缺效应和时间相关动力学。

IF 5.5 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-10-24 DOI: 10.1021/acs.jctc.5c01401

Carolin Joy,Igor Gaidai,Alexandre Faure,Dmitri Babikov

{"title":"Mixed Quantum/Classical Theory for Rotational Excitation of HDO in Collisions with H2: Symmetry Breaking Effects and Time-Dependent Dynamics.","authors":"Carolin Joy,Igor Gaidai,Alexandre Faure,Dmitri Babikov","doi":"10.1021/acs.jctc.5c01401","DOIUrl":"https://doi.org/10.1021/acs.jctc.5c01401","url":null,"abstract":"The application of the mixed quantum/classical theory of inelastic scattering (MQCT) to the rotational excitation of the isotopically substituted water molecule, HDO, in collisions with hydrogen molecules is presented. Modification of the potential energy surface of thewater + hydrogen system, due to isotopic substitution, is described, and the effect of symmetry breaking is explored. It is found that the additional terms of potential expansion are significant and, therefore, are expected to play an important role during the collision process. The modeling of HDO + H2 collision is carried out using both the MQCT method and the full-quantum CC method of MOLSCAT, using the latter as a reliable benchmark. Both para- and ortho-states of projectile H2 are considered. The focus is on those transitions that become allowed in HDO due to symmetry breaking, in contrast to the symmetric H2O where the para-ortho transitions are forbidden. Very good agreement between the two methods is observed, not only for the total but also for partial cross sections of rotationally inelastic transitions in HDO. Moreover, the time-dependent MQCT method offers an additional insight into the process of molecule-molecule collision, rotational state excitation, and energy transfer between the collision partners. It reveals an important role of the excited rotational states of the projectile H2 molecule and shows that, at certain values of collision impact parameters (or orbital angular momentum), the stepladder of sequential state-to-state transitions may lead to a surprising distribution of final state populations in HDO.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"20 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357807","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

Elastic Properties of Defective 2D Polymers from Regression Driven Coarse-Graining. 基于回归驱动粗粒化的缺陷二维聚合物弹性性能研究。

IF 5.5 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-10-23 DOI: 10.1021/acs.jctc.5c01339

David Bodesheim, Alexander Croy, Gianaurelio Cuniberti

引用次数: 0

Data-Driven Recommendation of Optimal Tuning Scheme for Range-Separated Hybrid Functionals in Solution-Phase UV/Vis Absorption Energy Prediction. 水溶液UV/Vis吸收能量预测中距离分离混合泛函最优调谐方案的数据驱动推荐。

IF 5.5 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-10-23 DOI: 10.1021/acs.jctc.5c01044

Fangning Ren, Pinyuan Li, Xu Chen, Lechen Dong, Fang Liu

{"title":"Data-Driven Recommendation of Optimal Tuning Scheme for Range-Separated Hybrid Functionals in Solution-Phase UV/Vis Absorption Energy Prediction.","authors":"Fangning Ren, Pinyuan Li, Xu Chen, Lechen Dong, Fang Liu","doi":"10.1021/acs.jctc.5c01044","DOIUrl":"https://doi.org/10.1021/acs.jctc.5c01044","url":null,"abstract":"Time-dependent density functional theory (TDDFT) combined with range-separated hybrid (RSH) functionals and a tuned range-separation parameter γ offers a computationally economical approach for high-throughput excited-state property predictions. The γ-tuning procedure in the gas phase is well established. However, no agreement on the best γ-tuning procedure has been made when considering the solvent effect with implicit solvent models like the polarizable continuum model (PCM). To answer that question, this study created a diverse dataset with 937 molecules with experimental solution-phase UV/vis absorption spectra. Three γ-tuning methods, the gas-phase γ-tuning (GPγT), the partial vertical γ-tuning (PVγT), and the strict vertical γ-tuning (SVγT), were evaluated for the ωPBEh functional over the entire dataset. Additional benchmarks are done for the optimally tuned screened range-separated hybrid combined with the PCM approach (SRSH-PCM) and the solvation-mediated tuning procedure (sol-med-OT). Our findings revealed that the optimal γ-values obtained by the PVγT and the SVγT are significantly smaller than the GPγT. This trend holds consistently across all molecules in our dataset, and we explained the origin of this phenomenon. TDDFT calculations with PVγT- and SVγT-tuned γ-values and default global Fock exchange fraction achieve superior performance compared to those using GPγT-tuned or default γ and slightly outperform SRSH-PCM and sol-med-OT with similar or lesser computational cost. Furthermore, we found that the smaller γ-values from SVγT captured the expected 1/(εR) asymptotic behavior in the solution phase, resulting in accurate prediction of solution-phase CT excitations, consistent with the screened asymptote behavior encoded in SRSH-PCM. These results show that SVγT is the best scheme for high-throughput UV/vis absorption spectrum calculations using the ωPBEh functional from a data-driven perspective.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353113","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

Defect-Driven Polaron Localization in π-Conjugated Systems: The Role of Spatial Correlation and Coulomb Binding. π共轭体系中缺陷驱动的极化子局域化：空间相关和库仑束缚的作用。

IF 5.5 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-10-23 DOI: 10.1021/acs.jctc.5c01418

Abhradeep Sarkar, Amiya Paul, Raja Ghosh

{"title":"Defect-Driven Polaron Localization in π-Conjugated Systems: The Role of Spatial Correlation and Coulomb Binding.","authors":"Abhradeep Sarkar, Amiya Paul, Raja Ghosh","doi":"10.1021/acs.jctc.5c01418","DOIUrl":"https://doi.org/10.1021/acs.jctc.5c01418","url":null,"abstract":"Defect engineering offers a powerful strategy to modulate polaron delocalization in π-conjugated materials; however, the complex interplay between different types of defects and dopant-induced Coulomb binding remains insufficiently understood. Here, we present a comprehensive theoretical investigation of hole-polaron transport using a Holstein-style Hamiltonian applied to π-conjugated lattices such as polymers and covalent organic frameworks (COFs) that incorporate vacancy and linker defects, a disorder framework encompassing distributions of disordered sites, and dopant-induced Coulomb binding effects. Simulated mid-infrared signatures and polaron coherence numbers uncover distinct and nuanced behaviors, revealing how the spatial correlation (random vs correlated) of different defect types governs polaron delocalization pathways. While dopant counterions strongly localize polarons, their precise positioning relative to crystalline versus disordered domains critically modulates transport efficiency. To establish experimental relevance, we compare our simulations with polarized intrachain and interchain mid-infrared spectra of doped P3HT films, providing fundamental insights into how specific dopant-polymer configurations give rise to anisotropic spectroscopic signatures and their direct correlation with anisotropic polaron transport. The strong agreement between theory and experiment validates our predictions and establishes guiding principles for optimizing polaron transport in disordered π-conjugated materials.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342105","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

Assessing Computational Strategies for the Evaluation of Antibody Binding Affinities. 评估抗体结合亲和力的计算策略。

IF 5.5 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-10-23 DOI: 10.1021/acs.jctc.5c01231

Ida Autiero,Damiano Buratto,Fengyi Guo,Wanding Wang,Malay Ranjan Biswal,Kevin C Chan,Ruhong Zhou,Francesco Zonta

{"title":"Assessing Computational Strategies for the Evaluation of Antibody Binding Affinities.","authors":"Ida Autiero,Damiano Buratto,Fengyi Guo,Wanding Wang,Malay Ranjan Biswal,Kevin C Chan,Ruhong Zhou,Francesco Zonta","doi":"10.1021/acs.jctc.5c01231","DOIUrl":"https://doi.org/10.1021/acs.jctc.5c01231","url":null,"abstract":"Accurate evaluation of binding affinity is critical in drug discovery to identify molecules that bind strongly to their targets while minimizing off-target effects. Although binding affinity calculations are theoretically well defined, they require exhaustive sampling of configurational space, a step that often requires significant computational resources. In this study, we compare different methods for calculating the binding energy of antibodies targeting a peptide derived from the N-terminus of CXCR2, a GPCR-family protein. Contrary to some previous reports, we find that equilibrium molecular mechanics Poisson-Boltzmann surface area (MMPBSA) calculations yield better agreement with experimental binding affinities than nonequilibrium potential of mean force evaluations, underscoring the system-dependent performance of these methods. We also observed a modest improvement in accuracy when MMPBSA is combined with replica exchange molecular dynamics, albeit at a significantly higher computational cost. Calculation based on the Rosetta force field, instead, produced results that did not correlate with the experimental data. We attribute these findings to two factors, which could limit the applicability of some methodologies that are widely used in computing the binding energy: the high potency of the antibodies studied and the dominance of hydrophobic interactions between the antibodies and the peptide. Overall, this work provides important insights for optimizing in silico antibody screening strategies.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"127 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339244","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

Knowles Partitioning from a Stationary Condition: Single- and Multireference Case. 平稳条件下的Knowles划分：单参考和多参考情况。

IF 5.5 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-10-22 DOI: 10.1021/acs.jctc.5c01147

Ágnes Szabados, András Gombás, Péter R Surján

引用次数: 0

Capturing Electron Correlation with Machine Learning through a Data-Driven CASPT2 Framework. 通过数据驱动的CASPT2框架捕获与机器学习的电子相关性。

IF 5.5 1区化学

Journal of Chemical Theory and Computation Pub Date : 2025-10-22 DOI: 10.1021/acs.jctc.5c01333

Grier M Jones, Konstantinos D Vogiatzis

引用次数: 0