Journal of Computational Chemistry最新文献

{"title":"Studying the Protein Thermostabilities and Folding Rates by the Interaction Energy Network in Solvent","authors":"Jun Liao,&nbsp;Mincong Wu,&nbsp;Fanjun Meng,&nbsp;Changjun Chen","doi":"10.1002/jcc.70113","DOIUrl":"https://doi.org/10.1002/jcc.70113","url":null,"abstract":"<div>\u0000 \u0000 <p>Residue interaction networks determine various characteristics of proteins, such as the folding rate, thermostability, and allosteric process. The interactions between residues can be described by distances or energies. The former is simple but less rigorous. The latter is complicated but more precise, especially when considering the solvent effect. In this work, we apply an existing energy decomposition method based on the Poisson–Boltzmann equation solver. The calculation is especially accelerated on GPU for higher performance. In four formal applications, the constructed interaction energy (IE) network shows good results. First, it is found that the protein folding rate has a stronger correlation with the energy-based contact order than the distance-based contact order. The Pearson correlation coefficient (PCC) is 0.839 versus 0.784 on a dataset of non-two-state proteins. Second, we find that most thermophilic proteins have lower IEs than mesophilic proteins. The IE in solvent acts as an indicator to evaluate the thermostabilities of proteins. Third, we use the IE network to predict the key residues in the formation of the insulin dimer. Most key residues are in agreement with the findings in previous alanine-scanning experiments. Lastly, we propose a novel method (called APFN) to predict the allosteric pathway based on the IE network. The method gives the same allosteric pathway for CheY protein as in previous nuclear magnetic resonance spectroscopy experiments. On the whole, the IE network in the solvent has been demonstrated to be reliable in describing the characteristics embedded in protein structures.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the Use of PDB X-Ray Crystal Structures as Force Field Target and Validation Data for Pyranose Ring Puckering","authors":"Olgun Guvench,&nbsp;Andrew L. Straffin","doi":"10.1002/jcc.70110","DOIUrl":"https://doi.org/10.1002/jcc.70110","url":null,"abstract":"<div>\u0000 \u0000 <p>The carbon and oxygen atoms of tetrahydropyran form the common substructure of pyranose monosaccharides in vertebrate glycans. This substructure can assume various ring puckering chair and skew-boat conformations, and can thereby impact glycan conformations relevant for biomolecular structure and signaling. The Protein Data Bank (PDB) provides a wealth of experimental glycan structural biology data that can be useful in the development and validation of molecular mechanics force fields for these molecules. However, these experimental data are typically from solvent-depleted crystalline environments at very low temperatures, in contrast to biological conditions that are aqueous and near ambient temperature, which is the regime targeted by biomolecular force fields. To determine if these PDB X-ray crystal data can be of utility as references for carbohydrate force fields, we compared ring puckering conformations from these experimental data to both vacuum and explicit aqueous solvent puckering free energy data from extended-system adaptive biasing force (eABF) molecular dynamics simulations using the previously validated CHARMM36 force field. We found that, for monosaccharides that are not charged (glucose, <i>N</i>-acetylglucosamine, galactose, <i>N</i>-acetylgalactosamine, mannose, xylose, and fucose), both the vacuum and aqueous simulation puckering preferences strongly correlate with PDB data, and therefore with each other. In contrast, all charged monosaccharides that were considered (the conjugate bases of <i>N</i>-acetylneuraminic acid, glucuronic acid, and iduronic acid) had puckering preferences correlating with PDB data only in aqueous simulations and not in vacuum simulations. These results suggest that comparing puckering preferences from aqueous simulations to PDB X-ray crystal puckering conformation data can be a valid and useful component of carbohydrate force field development and validation.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Giant Dipole Moments: Remarkable Effects Mono-, Di-, and Tri- Hydrated 5,6-Diaminobenzene-1,2,3,4-Tetracarbonnitrile","authors":"Katherine Stanley,&nbsp;R. Houston Givhan,&nbsp;Justin M. Turney,&nbsp;Henry F. Schaefer III","doi":"10.1002/jcc.70105","DOIUrl":"https://doi.org/10.1002/jcc.70105","url":null,"abstract":"<p>The molecule 5,6-diaminobenzene-1,2,3,4-tetracarbonnitrile (MOI) was first synthesized by Müllen and coworkers in 2016 and boasts an ultrastrong dipole moment of <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <mn>14.1</mn>\u0000 <mo>±</mo>\u0000 <mn>0.7</mn>\u0000 </mrow>\u0000 <annotation>$$ 14.1pm 0.7 $$</annotation>\u0000 </semantics></math> Debye in THF. Gas phase DFT computations do not fully reflect this ultrastrong dipole moment, demonstrating the role of solvent in increasing this dipole moment. Here, we investigate the effect of solvent molecule position on the dipole moment of this species, computationally examining systems with giant dipole moments. These systems are optimized in the gas phase with the B3LYP functional, employing the aug-cc-pVTZ and def2-TZVP basis sets, as well as the B3LYP-D3BJ/aug-cc-pVTZ functional in Orca. Single point DLPNO-CCSD/aug-cc-pVDZ results were obtained from Orca and Psi4, as well as DLPNO-CCSD(T)/CBS information from Psi4. Additionally, these are compared to the dipole moments of di- and tri-hydrated systems, and the SMD models for THF and water at the B3LYP/aug-cc-pVTZ level of theory. The dissociation energies, HOMO-LUMO energy gaps, and dipole moments are presented. These metrics show the nh1nh1′ THF system boasts the largest dissociation energy and dipole moment of the singly solvated systems, due to its strong hydrogen bonding. The importance of solvent placement is highlighted and may guide the synthesis of macromolecules or organic frameworks incorporating the MOI or MOI-like subunits. Remarkably, a single solvent molecule provides a good model for the difference between the gas phase and solvated species. The predicted gas phase dipole moments computed with B3LYP/aug-cc-pVTZ for the MOI, its monohydrated complex, dihydrated complex, and its trihydrated complex are 9.6, 14.2, 16.0, and 16.8 Debye, respectively.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IMPACT-4CCS: Integrated Modeling and Prediction Using Ab Initio and Trained Potentials for Collision Cross Sections","authors":"Carson Farmer,&nbsp;Hector Medina","doi":"10.1002/jcc.70106","DOIUrl":"https://doi.org/10.1002/jcc.70106","url":null,"abstract":"<p>Collision cross section (CCS) values can enhance the identification and classification of molecular contaminants such as per- and polyfluororoalkyl substances (PFAS). However, the computational burden required for large molecules, combined with the increasing number of potential PFAS candidates, can render existing methods incapable of providing sufficiently accurate results in a timely manner. Furthermore, machine learning methods struggle to generalize when the (de)protonated structure undergoes structural changes that are not common in the training dataset. In this study, we introduce IMPACT4-CCS (Integrated Modeling and Prediction using Ab initio and Trained potentials for Collision Cross Section), a novel computational workflow ensemble that comprises ab initio with machine learning tasks to accelerate accurate prediction of CCS for PFAS molecules. IMPACT-4CCS achieves comparable accuracy to current machine learning approaches, as validated using a test set of 100 molecules. Furthermore, IMPACT-4CCS exhibits better accuracy when implemented on some specific emerging PFAS subclasses, such as the <i>n</i>H-perfluoroalkyl carboxylic acids (<i>n</i>H-PFCA) family, for which other methods overestimate their CCS values. As far as the authors know, IMPACT-4CCS is the only existing method capable of capturing structural dynamics (i.e., hydrogen bridging) present in some large and flexible PFAS molecules. Our work demonstrates that the careful use of machine learning to accelerate traditional methods is likely to be more accurate than relying purely on machine learning on molecular graphs. Future (or recommended) work includes assessing the usefulness of IMPACT-4CCS for extending nontarget analysis to larger PFAS datasets such as the OECD (Organization for Economic Co-operation and Development) PFAS list in PubChem, which could be greater than 7 million molecules with diverse chemistry.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling Reaction Path Bifurcation: Insights Into Electron Movement via Natural Reaction Orbitals","authors":"Tatsuhiro Nakanishi,&nbsp;Takuro Tsutsumi,&nbsp;Yuriko Ono,&nbsp;Kazuki Sada,&nbsp;Tetsuya Taketsugu","doi":"10.1002/jcc.70101","DOIUrl":"https://doi.org/10.1002/jcc.70101","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigates the Beckmann rearrangement of 1-phenyl-2-propanone oxime derivatives, focusing on the reaction path bifurcation behavior from the perspective of electron movement. The previous work reported that electron-withdrawing substituents drove the reaction toward the rearrangement pathway, while electron-donating substituents favored the fragmentation pathway. Through natural reaction orbital (NRO) analysis, this research demonstrates how electrons move at critical branching points, specifically in the directions of the intrinsic reaction coordinate (IRC) and the projected vibrational mode associated with the branching behavior. The NRO approach, which complements traditional IRC and ab initio molecular dynamics methods, not only provides valuable quantitative insights for predicting product distributions but also aids in the strategic design of substituents for desired products. These findings extend our understanding of reaction mechanisms and byproduct formation, offering fresh perspectives on complex chemical transformations.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MolRWKV: Conditional Molecular Generation Model Using Local Enhancement and Graph Enhancement","authors":"Xihan Li,&nbsp;Kuanping Gong,&nbsp;Yongquan Jiang,&nbsp;Yan Yang,&nbsp;Tianrui Li","doi":"10.1002/jcc.70100","DOIUrl":"https://doi.org/10.1002/jcc.70100","url":null,"abstract":"<div>\u0000 \u0000 <p>Conditional-based molecule generation techniques help to provide molecules with specific conditions for practical applications. As the SMILES string is represented as a sequence of strings, it can be processed using a language model that gradually generates its complete sequence by employing a loop to generate the next token. The efficient parallelism and efficient reasoning ability of RWKV indicate its potential for success in the field of natural language processing. Therefore, we proposed the MolRWKV de novo conditional molecule generation model, which integrates CNN and GCN based on the RWKV model, combining the ability of CNN to extract local information of SMILES sequences and the ability of GCN to obtain topological structure information of molecular graphs. Experiments show that MolRWKV can achieve comparable results to existing models in both unconditional and conditional generation, improve the accuracy of conditional generation, generate diverse molecules while retaining scaffold information, and generate molecules with affinity for specific target proteins.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Docking Survey, ADME, Toxicological Insights, and Mechanistic Exploration of the Diels–Alder Reaction Between Hexachlorocyclopentadiene and Dichloroethylene","authors":"Agnieszka Kącka-Zych,&nbsp;Abdellah Zeroual,&nbsp;Asad Syed,&nbsp;Ali H. Bahkali","doi":"10.1002/jcc.70092","DOIUrl":"https://doi.org/10.1002/jcc.70092","url":null,"abstract":"<div>\u0000 \u0000 <p>The Diels–Alder (DA) reaction between hexachlorocyclopentadiene and 1,2-dichloroethylene has been studied using the Molecular Electron Density Theory (MEDT) through Density Functional Theory (DFT) calculations at the B3LYP/6−31G(d) level. The electronic structure of the reagents has been characterized through the electron localization function (ELF) and the conceptual DFT (CDFT). The DA reaction of hexachlorocyclopentadiene with 1,2-dichloroethylene proceeds via a synchronous or low asynchronous one-step mechanism. Based on the conducted research, a two-step mechanism with a biradical intermediate was completely ruled out. Bonding Evolution Theory (BET) study of the DA reaction shows that this reaction is topologically characterized by nine different phases. The reaction begins with the rupture of the double bonds in substrate molecules. Formation of the first C<span></span>C single bond takes place in phase VII, while the second C<span></span>C single bond takes place in phase IX. Formation of these two single bonds takes place by sharing the nonbonding electron densities of the two pairs of <i>pseudoradical</i> centers. In addition, this study evaluates some ligands as potential HIV-1 inhibitors. Docking results identified <b>5</b> and <b>5-F</b> as the most promising candidates, surpassing AZT in theoretical affinity. ADME analysis revealed limitations in solubility and absorption for compounds <b>3</b>, <b>4</b>, and <b>5</b>, while <b>5-F</b> showed better solubility but low absorption. Toxicity concerns around <b>5-F</b> suggest the need for risk management, while the other compounds require further safety assessment.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Relation Between the Excited Electronic States of Acene Radical Cations and Neutrals—A Computational Analysis","authors":"Anna M. Weidlich,&nbsp;Andreas Dreuw","doi":"10.1002/jcc.70095","DOIUrl":"https://doi.org/10.1002/jcc.70095","url":null,"abstract":"<p>Acenes are a class of molecules that enjoy popularity in both experimental and theoretical fields of research for their diverse areas of application and unique electronic structure. One particular aspect of interest lies in their electronic absorption spectra, which have been thoroughly investigated both experimentally and theoretically. In this work, the electronically excited states of radical cations of acenes from naphthalene to dodecacene are investigated using algebraic diagrammatic construction (ADC) methods and different time-dependent density functional theory (TD-DFT) exchange-correlation kernels. The performance of the employed ADC methods and different DFT functionals is assessed using experimental values as benchmarks. Using ADC, it is then shown that excited states typical for neutral acenes are retained in their radical cation counterparts, while additional states emerge due to excitations into the singly-occupied molecular orbital (SOMO). Finally, the evolution of the excitation energies in neutral as well as cationic acenes with increasing length is investigated using TD-DFT, where a special focus lies on the correct description of longer acenes using single-reference methods.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing MM/P(G)BSA Methods: Integration of Formulaic Entropy for Improved Binding Free Energy Calculations","authors":"Lina Dong,&nbsp;Pengfei Li,&nbsp;Binju Wang","doi":"10.1002/jcc.70093","DOIUrl":"https://doi.org/10.1002/jcc.70093","url":null,"abstract":"<div>\u0000 \u0000 <p>Balancing computational efficiency and precision, MM/P(G)BSA methods have been widely employed in the estimation of binding free energies within biological systems. However, the entropy contribution to the binding free energy is often neglected in MM/P(G)BSA calculations, due to the computational cost of conventional methods such as normal mode analysis (NMA). In this work, the entropy effect using a formulaic entropy can be computed from one single structure according to variations in the polar and non-polar solvents accessible surface areas and the count of rotatable bonds in ligands. It was incorporated into MM/P(G)BSA methods to enhance their performance. Extensive benchmarking reveals that the integration of formulaic entropy systematically elevates the performance of both MM/PBSA and MM/GBSA without incurring additional computational expenses. In addition, we found the inclusion of dispersion can deteriorate the correlation performance (<i>R</i>_<i>p</i>) but reduce the root mean square error (RMSE) of both MM/PBSA and MM/GBSA. Notably, MM/PBSA_S, including the formulaic entropy but excluding the dispersion, surpasses all other MM/P(G)BSA methods across a spectrum of datasets. Our investigation furnishes a valuable and practical MM/P(G)BSA method, optimizing binding free energy calculations for a variety of biological systems.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can Water Trigger Room-Temperature Formation of Benzofuran-2(3H)-one Scaffolds From Vinyldiazene Derivatives? Computational Insights Into an Unusual Cyclization","authors":"Ulviyya Askerova,&nbsp;Yusif Abdullayev,&nbsp;Namiq Shikhaliyev,&nbsp;Avtandil Talybov,&nbsp;Jochen Autschbach","doi":"10.1002/jcc.70102","DOIUrl":"https://doi.org/10.1002/jcc.70102","url":null,"abstract":"<div>\u0000 \u0000 <p>Access to benzofuran-2(3H)-one derivatives from readily available substrates under mild conditions is crucial in the pharmaceutical and plastics industries. We identified (Z)-3-(2-phenylhydrazineylidene)benzofuran-2(3H)-one (<b>P</b>) during the recrystallization of (E)-2-(2,2-dichloro-1-(phenyldiazenyl)vinyl)phenol using a 96% ethanol solution. The mechanism of the unexpected substrate conversion leading to <b>P</b> is investigated using density functional calculations. The computations revealed that ethanol is required to initiate the reaction via <b>TS1E</b>, which involves a concerted deprotonation of ethanol by the basic diaza group of the substrate and an ethoxy group attacking the electrophilic center (Cl₂C), with an energy barrier of 28.3 kcal/mol. The resulting intermediate (<b>I1E</b>) is calculated to be unstable and can yield a cyclic chloroacetal adduct with a lower energy barrier of 2.2 kcal/mol via the ring-closure transition state (<b>TS2E</b>). In the absence of water, the next steps are impossible because water is required to cleave the ether bond, yielding <b>P</b>. A small amount of water (4% of the recrystallization solvent) can promote further transformation of <b>I2E</b> via the transition states <b>TS3E</b> (∆<i>G</i>^‡ = 11.1 kcal/mol) and <b>TS4E</b> (∆<i>G</i>^‡ = 10.5 kcal/mol). A comparison of the ethanol/water- and only water-promoted free energy profiles shows that the presence of ethanol is crucial for lowering the energy barriers (by about 5 kcal/mol) for the initial two steps leading to the cyclic chloroacetal (<b>I2E</b>), whereas water is then required to initiate product formation.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}