Journal of Computational Chemistry最新文献

{"title":"Unveiling Hidden Intramolecular Non-Covalent Interactions in a Neutral Serine, Its Zwitterion, Cluster, and Crystal by Features of Electron Density","authors":"Vasilii Korotenko,&nbsp;Anna Egorova,&nbsp;Vladimir Tsirelson","doi":"10.1002/jcc.70134","DOIUrl":"https://doi.org/10.1002/jcc.70134","url":null,"abstract":"<p>We investigate intramolecular non-covalent interactions (NCIs) in neutral serine, its zwitterion, molecular clusters, and crystal using electron density-based approaches, including QTAIM, RDG, IQA, and electronic pressure analysis. In addition to completed NCIs (hydrogen bonds with bond paths), we identify latent interactions—attractive, bond-path-free atomic pair interactions with negative interaction energies. These are classified into <i>dynamic</i> (vibration-induced and transient) and <i>static</i> (secondary, persistent but structurally passive) types. Analysis of the internal pressure in electronic continuum reveals that latent NCIs exhibit distinct signatures in the kinetic and exchange components, which evolve across the molecular, cluster, and crystalline states. <i>Dynamic</i> interactions are characterized by off-axis minima in the exchange part of the pressure, whereas <i>static</i> interactions lack such features. Upon crystallization, intramolecular latent NCIs may disappear due to electron density redistribution and the formation of intermolecular hydrogen bonds. These intermolecular contacts may also spatially constrain atoms, suppressing vibrational flexibility and effectively converting <i>dynamic</i> NCIs into <i>static</i> ones. The kinetic pressure highlights regions of electron localization, while the exchange pressure offers a physical criterion for distinguishing different types of NCIs. Our findings demonstrate the structural and stabilizing roles of latent interactions and establish electronic pressure as a sensitive and informative descriptor for their analysis.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 17","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514701","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":"Unlocking the Conformational Secrets of DYRK1A Kinase With Computational Microscope: Exploring Phosphorylation-Driven Structural Dynamics","authors":"Kapil Dattatray Ursal,&nbsp;Md Fulbabu Sk,&nbsp;Subhasmita Mahapatra,&nbsp;Parimal Kar","doi":"10.1002/jcc.70172","DOIUrl":"https://doi.org/10.1002/jcc.70172","url":null,"abstract":"<div>\u0000 \u0000 <p>The intricate world of cellular processes relies significantly on the dual-specificity tyrosine-phosphorylation-regulated kinase (DYRK) family of kinases, governing vital functions like brain development, splicing regulation, and apoptosis. DYRK1A, in particular, stands at the center of attention due to its pivotal role. Disruptions in its activity, whether through upregulation or downregulation, have profound implications, notably in neurological disorders and cancer progression. Understanding the impact of phosphorylation, a fundamental post-translational modification, on DYRK1A is paramount. In this study, we delved into the complex interplay of phosphorylation and the effects of the abemaciclib inhibitor on DYRK1A conformational dynamics. We employed advanced techniques such as molecular dynamics simulations and the molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) scheme and deciphered the intricate dance of DYRK1A's structural elements during phosphorylation. Our exploration revealed intriguing details: the <i>α</i>C-helix undergoing outward movement, a distorted <i>α</i>C-helix, a wide-open P-loop, extended A-loop, and role of electrostatic interactions shaping A-loop dynamics. Notably, the interaction of specific residues, particularly Lys¹⁸⁸, forming robust salt bridges with Asp³⁰⁷ and Glu²⁰³, plays a pivotal role in shaping the structure of the protein. Diving deeper, we conducted principal component analysis and conformational free energy sampling to uncover crucial structural intermediates. Moreover, our dynamic cross-correlation map sheds light on the influence of phosphorylation by enhancing coordinated movements while dampening anti-correlated motions across various domains. This nuanced understanding of DYRK1A kinase activation, driven by phosphorylation, not only enriches our knowledge but also holds promise in the development of targeted therapies for associated diseases.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 17","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515006","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":"LOPOSTER: A Cascading Postprocessor for LOBSTER","authors":"YiXu Wang,&nbsp;Peter C. Müller,&nbsp;David Hemker,&nbsp;Richard Dronskowski","doi":"10.1002/jcc.70167","DOIUrl":"https://doi.org/10.1002/jcc.70167","url":null,"abstract":"<p>The computer program LOPOSTER, available via GitHub, is introduced, capable of postprocessing the LOBSTER code results. LOPOSTER is designed to be particularly effective for analyzing large datasets with over 10,000 interactions and enormously reducing postprocessing time. LOPOSTER pioneers the automated processing of advanced bonding analysis results, including multicenter bonding, molecular-orbital formation energy, and <i>k</i>-dependent COHP, expanding the scope of routine chemical-bonding investigations. In addition, LOPOSTER streamlines the postprocessing workflow by providing comprehensive results in a single execution, minimizing user intervention and potential errors. An example of chemical-bonding analysis on NiNCN is provided, with visualization by LOPOSTER. LOPOSTER offers versatile analysis of interactions in NiNCN, enabling evaluations in real or reciprocal space, and based on atomic or molecular orbitals, catering to different analytic preferences. Various correlations between those interactions and magnetism in NiNCN are also explored. The electron-rich features of an N=C=N π bond have been discussed from various perspectives.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 17","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514702","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":"Extremely High RAHB Energies Quantified via a Molecular Tailoring Approach in Fused-Ring Tropolones and Their Effect on the Electronic Structure and Optical Properties","authors":"Andrei V. Afonin,&nbsp;Danuta Rusinska-Roszak,&nbsp;Alexander V. Vashchenko","doi":"10.1002/jcc.70153","DOIUrl":"https://doi.org/10.1002/jcc.70153","url":null,"abstract":"<div>\u0000 \u0000 <p>The O<span></span>H···OC RAHB energies were quantified via a molecular tailoring approach for a series of tropolones with the fused aromatic and antiaromatic cycles. At 3,4 and 5,6 fusions of the tropone ring with aromatic cycles, the RAHB enhancement is observed while the RAHB weakening takes place at 4,5 and 6,7 fusions. An opposite trend appears at the fusion of the tropone ring with the antiaromatic cycle. A linear ratio was found between the HOMA structure-based aromaticity indices as well as NICS magnetic ones for the tropone ring and the RAHB energy. The total RAHB energy is divided into σ- and π-components. The σ- and π-components were established to change in the same directions, appearing the synergism. This synergism causes extremely high RAHB energies above 30 kcal/mol in some tropolones. It was shown that RAHB acquires the features of CAHB in these cases due to the excess charge on the oxygen of the CO group. The influence of the RAHB strength on the frontier molecular orbitals patterns, energy, the size of the gap between them, and the <i>λ</i>_max absorption wavelength in the UV/vis range was studied. It was revealed that the HOMO energy elevates, the LUMO energy lowers, the HOMO-LUMO gap narrows, and the <i>λ</i>_max wavelength undergoes a bathochromic shift with RAHB strengthening in the studied tropolones.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 17","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514957","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":"Conformational Changes and Free Energy Landscape of the Unbinding of External Aldimine at the Active Site of Ornithine Decarboxylase in Aqueous Medium","authors":"Shreya Rastogi,&nbsp;Amalendu Chandra","doi":"10.1002/jcc.70165","DOIUrl":"https://doi.org/10.1002/jcc.70165","url":null,"abstract":"<div>\u0000 \u0000 <p>The pyridoxal-5′-phosphate (PLP)-dependent enzymes constitute an important class of enzymes that undergo crucial conformational changes between their apo and holo forms, which are essential for their functional versatility. In this study, we have investigated the conformational changes of ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, and the unbinding of the PLP-substrate complex (external aldimine) at the active site of the enzyme using molecular dynamics and well-tempered metadynamic simulations. The study reveals a three-step mechanism for the ligand unbinding process. Initially, the enzyme undergoes a reorganization in which the distance between the C-terminal and N-terminal domains of opposite chains that form the active site increases. This reorganization opens the active site, and the interactions between the PLP-substrate complex and two active site loops, namely loop1 and loop2, begin to weaken. As a result, the ligand exits the active site and primarily interacts with loop3. Over time, these interactions with loop3 also weaken, and the ligand eventually becomes fully unbound. The calculated free energy differences for these steps are found to be 1 kcal/mol, 6 kcal/mol, and 8 kcal/mol, respectively. Our findings provide detailed insights into the conformational changes and energetics associated with ligand unbinding in ODC, offering a valuable framework for understanding similar processes in other PLP-dependent enzymes.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 17","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492954","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":"Iterative Implementation of the Dipole Interaction Model for Atomic Polarizabilities","authors":"Raphael F. Ligorio,&nbsp;Leonardo H. R. Dos Santos,&nbsp;Anna Krawczuk","doi":"10.1002/jcc.70158","DOIUrl":"https://doi.org/10.1002/jcc.70158","url":null,"abstract":"<p>Despite its name, the dipole interaction model (DIM) serves not only to adjust dipole moments due to atomic interactions but also to assess polarizabilities. Traditionally, polarizability calculations via DIM rely on matrix inversion, posing constraints on memory usage and computational time. Recent implementations have shown significant performance boosts by employing an iterative inversion solver, albeit reducing accuracy. In this paper, we present a direct approach for computing polarizabilities via iterative cycles, eliminating the need for matrix inversion. This allows for scaling up the model to hundreds of thousands of atoms without sacrificing precision, as often happens when simplifying the standard inversion procedure to reduce computational costs. Additionally, we have addressed memory issues associated with storing extensive arrays in standard implementations. Our advancement holds promise for diverse applications, providing an efficient method for exploring polarizabilities in various systems.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 17","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492952","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":"Evaluation of Physics-Based Protein Design Methods for Predicting Single Residue Effects on Peptide Binding Specificities","authors":"Merve Ayyildiz,&nbsp;Jakob Noske,&nbsp;Florian J. Gisdon,&nbsp;Josef P. Kynast,&nbsp;Birte Höcker","doi":"10.1002/jcc.70160","DOIUrl":"https://doi.org/10.1002/jcc.70160","url":null,"abstract":"<p>Understanding the interactions that make up protein–protein or protein-peptide interfaces is a crucial step towards applications in biotechnology. The mutation of a single residue can have a strong impact on binding affinity and specificity, which is difficult to capture in sampling and scoring. Many established computational methods provide an estimate of binding or non-binding; however, comparing highly similar ligands is an important and significantly more challenging problem. Here we evaluated the capability of predicting ligand binding specificity using three established but conceptually different physics-based methods for protein design. As a model system, we analyzed the binding of peptides to designed armadillo repeat proteins, where a single residue of the peptide was changed systematically, leading to affinity changes in the range of 1–1000 nM. We critically assessed the prediction accuracy of the computational methods. While a good correlation with experimentally determined data was observed in several cases, specific biases in the prediction performance of each method were identified.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 17","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492965","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":"When Simulations Meet Machine Learning: Redefining Molecular Docking for Protein-Glycosaminoglycan Systems","authors":"Krzysztof K. Bojarski","doi":"10.1002/jcc.70161","DOIUrl":"https://doi.org/10.1002/jcc.70161","url":null,"abstract":"<div>\u0000 \u0000 <p>Glycosaminoglycans (GAGs) are linear, negatively charged carbohydrates that modulate enzymatic activity in the extracellular matrix. Their high flexibility and specificity in protein-GAG interactions pose challenges for both experimental and computational studies. Here, the repulsive scaling replica exchange molecular dynamics (RS-REMD) method, combined with molecular mechanics generalized born surface area (MM-GBSA), was implemented using the CHARMM36m force field to evaluate its ability to guide ligands to their native binding sites in seven protein-GAG/carbohydrate complexes. A five machine learning (ML)-based models including fully connected neural network (FCNN), linear regression, LightGBM, random forest and support vector regressor (SVR) were also trained to predict binding accuracy (RMSatd) based on MM-GBSA energy components, protein-GAG distances, and hydrogen bond counts. While MM-GBSA values showed weak to moderate correlations with RMSatd, most of the trained AI models significantly improved the selection of native-like binding poses with Random Forest model providing most accurate predictions. This study highlights the potential of integrating simulations with ML to refine molecular docking for flexible ligands like GAGs.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 17","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472876","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":"pyHRSOA and pyTHSOA: Postprocessing Codes for the Computation of Second and Third-Order Scattering Optical Activities","authors":"Andrea Bonvicini,&nbsp;Benoît Champagne","doi":"10.1002/jcc.70149","DOIUrl":"https://doi.org/10.1002/jcc.70149","url":null,"abstract":"<div>\u0000 \u0000 <p>We present <span>pyHRSOA</span> and <span>pyTHSOA</span>, two postprocessing Python codes for the computation of the circular differential scattering ratio, a dimensionless quantity which is the central observable for two novel and promising nonlinear chiroptical techniques: the hyper-Rayleigh scattering optical activity (HRS-OA) and the third-harmonic scattering optical activity (THS-OA) spectroscopies. From a computational point of view, the simulation of the HRS-OA (THS-OA) spectroscopy requires the calculations of five first (second) hyperpolarizabilities and these can be obtained from quadratic (cubic) responses functions by using the DALTON quantum chemistry software. However, the expressions for the chiral and achiral contributions to the scattered intensities are quite complicated because these contain a lot of terms. In particular, for HRS-OA and THS-OA 30 and 46 molecular invariants need to be computed, thus complicating their computational implementation. The postprocessing codes presented here can be used as black-box tools for the simulations of HRS-OA and THS-OA spectroscopies. The source codes are available at https://gitlab.unamur.be/abonvici/pyhrsoa_pythsoa (DOI 10.5281/zenodo.15424494).</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 17","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482270","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":"Simplistic Software for Analyzing Mass Spectra and a Mixed Experimental-Theoretical Database for Identifying Poisonous and Explosive Substances","authors":"Denis S. Tikhonov,&nbsp;Mikhail A. Kalinin,&nbsp;Alexander A. Maryewski,&nbsp;Aleksandr A. Avdoshin,&nbsp;Olgert Dallakyan,&nbsp;Nikita A. Vasilev,&nbsp;Egor A. Eliseev,&nbsp;Mandy Koch,&nbsp;Vladimir V. Rybkin,&nbsp;Denis G. Artiukhin","doi":"10.1002/jcc.70148","DOIUrl":"https://doi.org/10.1002/jcc.70148","url":null,"abstract":"<p>A recent increase in targeted attacks using chemical warfare agents by dictators and authoritarian regimes against politicians, journalists, and other civilians is a major concern. To aid the civil investigators in identifying poisonous substances in such cases, we developed an algorithm and a lightweight and simple-to-use software, <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <mtext>ToxicMassSceptic</mtext>\u0000 </mrow>\u0000 <annotation>$$ mathtt{ToxicMassSceptic} $$</annotation>\u0000 </semantics></math>, with a database of 400 electron ionization mass spectra entries, which include many poisonous and explosive agents. The identification relies on a window-based reduction of the experimental spectra and four statistical metrics that are combined into a single metametric. The software also features automatic spectral background removal. Furthermore, we provide the workflow for increasing the size of this database by performing theoretical calculations of mass spectra with a molecular dynamics-based approach. The accuracy of both the theoretical prediction workflow and <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <mtext>ToxicMassSceptic</mtext>\u0000 </mrow>\u0000 <annotation>$$ mathtt{ToxicMassSceptic} $$</annotation>\u0000 </semantics></math> is validated on the experimental spectra. Our results demonstrate that the proposed software package can aid in the preliminary identification of traces of poisonous and explosive substances.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 17","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472875","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}