Journal of Molecular Modeling最新文献

{"title":"Substituent effects on the thermal stability and initial decomposition of methylene bis(dinitropyrazole) derivatives","authors":"Yuqin Chu,&nbsp;Peng Zhang,&nbsp;Yang Zhu,&nbsp;Peng Ma,&nbsp;Congming Ma","doi":"10.1007/s00894-026-06974-3","DOIUrl":"10.1007/s00894-026-06974-3","url":null,"abstract":"<div><h3>Context</h3><p>Elucidating the role of functional-group substitution in the thermal stability of energetic materials is of considerable importance for the rational development of advanced energetic compounds. In this study, density functional theory (DFT) calculations, together with electronic-structure, weak-interaction, crystal-packing, and transition-state analyses, were performed to systematically explore the influence of amino (A), hydroxyl (B), and azido (C) substituents on methylene-bridged bis(3,5-dinitropyrazole) (MBDNP) derivatives. The results reveal that functional-group substitution induces distinct electronic redistribution, leading to significant differences in key bond stability, intra- and intermolecular interactions, and crystal packing. Among the three derivatives, A exhibits the strongest electron delocalization, the most favorable interaction network, and the strongest intermolecular interactions, whereas C shows the weakest molecular and crystal stability. Transition-state calculations further demonstrate that different substituents alter the preferred initial decomposition pathways, and the calculated activation free energies follow the order A &gt; B &gt; C, consistent with the experimentally observed decomposition temperatures. These findings demonstrate that the thermal stability of MBDNP derivatives is governed by the synergistic effects of electronic structure, molecular interactions, crystal packing, and initial decomposition kinetics, providing molecular-level insights into the substituent-dependent thermal decomposition mechanism of energetic materials.</p><h3>Methods</h3><p>Density functional theory (DFT) calculations at the M06-2X/def2-TZVPP level were performed to investigate the electronic structures and initial decomposition behavior of compounds A–C. Natural bond orbital (NBO), electrostatic potential (ESP), localized bond order (LBO), interaction region indicator (IRI), and quantum theory of atoms in molecules (QTAIM) analyses, together with Hirshfeld surface, energy framework, and transition-state analyses, were further performed to clarify how different substituents influence the electronic characteristics, intermolecular interactions, crystal-packing behavior, and thermal stability of the studied compounds.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theoretical studies to understand the (textrm{OH}^{bullet }) and (textrm{CH}_{3}{}^bullet ) radical scavenging mechanisms of an antioxidant: pheophorbide a (Phe a)","authors":"Monorama Kalowar,&nbsp;Swarnadeep Biswas","doi":"10.1007/s00894-026-06967-2","DOIUrl":"10.1007/s00894-026-06967-2","url":null,"abstract":"<div><h3>Context</h3><p>Hydroxyl (<span>(textrm{OH}^bullet )</span>) and methyl (<span>(textrm{CH}_{3}{}^bullet )</span>) radicals are reactive species that induce oxidative damage to important biomolecules and contribute to various diseases. Exogenous antioxidants and those present in our bodies use various mechanisms, including scavenging of reactive species, to prevent oxidative stress. Therefore, identifying efficient natural antioxidants capable of scavenging these radicals is of considerable interest. In this work, the antioxidant activity of pheophorbide a (Phe a), a chlorophyll a derivative, was comprehensively investigated to understand the mechanisms of radical scavenging, including radical adduct formation (RAF), hydrogen atom transfer (HAT), and single-electron transfer (SET). Thermodynamic analysis indicates that RAF and HAT are the preferred radical-scavenging pathways, whereas the SET pathway is thermodynamically unfavourable. Kinetic analysis further demonstrates that RAF is the kinetically more favourable pathway for both radicals investigated. Frontier molecular orbital analysis, molecular electrostatic potential (MEP) mapping, and global quantum chemical descriptors identified the most reactive sites and further support the antioxidant activity of Phe a.</p><h3>Methods</h3><p>Density functional theory (DFT) calculations were performed using the M06-2X functional present in the Gaussian 09 software package. Geometry optimisations and frequency calculations for the RAF, HAT, and SET pathways were carried out with 6-31G(d) basis set in the gaseous phase, followed by single-point energy calculations at the M06-2X/6-311+G(d,p) level of theory in gaseous and aqueous phases. Solvent effects were included using the polarizable continuum model (PCM). The reaction free energies (<span>(Delta G_f)</span>) are calculated to investigate the feasibility of the reactions involved in our study. Activation free energies (<span>(Delta G^{b})</span>) were calculated for the RAF and HAT mechanisms. The corresponding rate constants were determined using transition state theory, incorporating standard-state, Wigner tunnelling, diffusion, and degeneracy corrections. Molecular structures, molecular orbital surfaces, and the vibrational frequencies of the molecules were visualised using GaussView 5.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A molecular modeling and machine learning–based approach for the identification of potential human ALOX15 inhibitors","authors":"Sonam Grewal,&nbsp;Biswayan Ghosh,&nbsp;Roy Karnati,&nbsp;Tanneru Hemanth Kumar,&nbsp;Polamarasetty Aparoy","doi":"10.1007/s00894-026-06968-1","DOIUrl":"10.1007/s00894-026-06968-1","url":null,"abstract":"<div><h3>Context</h3><p>Arachidonate 15-lipoxygenase (ALOX15) metabolises polyunsaturated fatty acids into lipid mediators that regulate inflammation. Depending on the cell type and substrate, ALOX15 influences both pro-inflammatory and pro-resolving pathways. Its dysregulation is associated with asthma, atherosclerosis, neurodegeneration, ferroptosis, inflammation, oxidative stress and disrupted lipid homeostasis. Therefore, targeting ALOX15 offers a promising strategy for modulating pathological lipid oxidation.</p><h3>Method</h3><p>In this study, a hybrid ligand-based and structure-based machine learning (ML) framework was developed that combines physicochemical and 3D ligand features with interacting features (including SIFts) derived from protein-ligand interactions for the discovery of putative ALOX15 inhibitors. To identify potent human ALOX15 inhibitors, predictive machine learning (ML) models were developed, a dataset was obtained from BindingDB and multiple molecular representations (1-D, 2-D, 3-D descriptors, fingerprints and post-docking features) were computed. Two classes of ML models, Type A and Type B, were developed using 8 regression algorithms. The best Type A model, XGBoost, achieved training <i>R</i>² of 0.915 (RMSE = 0.299; MAE = 0.224) and test <i>R</i>² of 0.688 (RMSE = 0.581; MAE = 0.456), whereas the best Type B model, Random Forest, attained training <i>R</i>² of 0.938 (RMSE = 0.254; MAE = 0.195) and test <i>R</i>² of 0.659 (RMSE = 0.607; MAE = 0.473). Over 5 million compounds from various databases were screened, and five compounds were identified. ADME predictions and molecular dynamics simulations suggest favourable pharmacokinetic properties and stable binding within the active site of human ALOX15. These compounds are proposed as putative inhibitors and require further experimental validation.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Derivatives of dPMTO, dMTMO, and dTPT3 as efficient genetic alphabets for artificial DNA","authors":"N. R. Jena,&nbsp;R. Daheriya,&nbsp;A. K. Singh","doi":"10.1007/s00894-026-06966-3","DOIUrl":"10.1007/s00894-026-06966-3","url":null,"abstract":"<div><h3>Context</h3><p>The stability of natural DNA relies mainly on the hydrogen-bonding interactions between its nucleobases. However, recently, several hydrophobic nucleobases, such as dPTMO, dMTMO, and dTPT3, were synthesized to expand the genetic codes that do not make hydrogen-bonding base pair interactions in DNA. Although such bases were recognized by DNA polymerases during replication, the artificial DNA was found to be unstable and to contain intercalated bases. To make stable artificial DNA that can be recognized by DNA polymerases, dPTMO, dMTMO, and dTPT3 were modified to contain hydrophilic groups at their Watson–Crick faces. In doing so, 25 derivatives of dPTMO, 33 derivatives of dMTMO, and 31 derivatives of dTPT3 were generated that can form hydrogen-bonding interactions in DNA. Subsequently, base pair interactions between different derivatives of dPTMO and dTPT3 and between different derivatives of dMTMO and dTPT3 were studied to identify the most stable purine:pyrimidine base pairs. Interestingly, 16 base pairs are identified to be more stable than the three hydrogen-bonded canonical G:C pair, among which dPTMO-20:dTPT3-19, dPTMO-21:dTPT3-19, dMTMO-28:dTPT3-19, and dMTMO-29:dTPT3-19 were found to be highly stable, with binding energy lying between -22 and -23 kcal/mol. It is thus proposed that hybrid bases, such as dPTMO-20, dPTMO-21, dMTMO-28, dMTMO-29, and dTPT3-19, would serve as effective artificial bases to expand the genetic alphabet.</p><h3>Methods</h3><p>The ωB97X-D/6–31 + G* level of dispersion-corrected Density Functional Theory was employed to generate derivatives of dPTMO, dMTMO, and dTPT3 by modifying their Watson–Crick faces with various hydrogen-bond donors and acceptors, enabling them to form hydrogen-bonding interactions. Subsequently, 174 base pair structures were optimized at the same level of theory to identify the canonical G:C-like base pairs. All structures were optimized in the aqueous medium by employing the Integral Equation Formalism of the Polarized Continuum Model (IEFPCM) of the Self-Consistent Reaction Field (SCRF) theory. To get more accurate binding energies, the ωB97X-D/AUG-cc-pVDZ level of theory was used to compute the single-point energy values in the aqueous medium.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A stable tensorial approach for inversion of adsorption potential energy from isotherm data","authors":"Márcio Oliveira Alves,&nbsp;Felipe Silva Carvalho,&nbsp;João Pedro Braga","doi":"10.1007/s00894-026-06963-6","DOIUrl":"10.1007/s00894-026-06963-6","url":null,"abstract":"<div><h3>\u0000 <b>Context</b>\u0000 </h3><p>Underlying the adsorption mechanism is not a simple task due to the complexity of the process. In this context, statistical mechanics provides a versatile approach with relatively low computational cost for describing adsorption phenomena. An alternative strategy consists of obtaining the adsorption potential energy from experimental data through the solution of an inverse problem. In this work, the adsorption potential energy was determined directly from adsorption isotherms using experimental datasets for both aqueous- and gas-phase adsorption systems. The proposed methodology was compared with the traditional two-step procedure, in which the second adsorption virial coefficient is first determined and subsequently used for inversion of the potential energy. Due to the ill-posed nature of the problem, the conventional approach exhibits significant instability and error propagation. In contrast, the direct inversion method provides excellent results, achieving values of <span>(R^2 sim 0.99)</span>.</p><h3>\u0000 <b>Methods</b>\u0000 </h3><p>A methodology grounded in statistical physics was developed to obtain the adsorption potential energy directly from isotherm data. The proposed approach formulates the problem as a tensor contraction, eliminating the need for the traditional two-step procedure involving the intermediate determination of the second adsorption virial coefficient.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the chemical space of Bcl-2 inhibitors: a multiscale computational exploration of the benzopyran (chromene) scaffold","authors":"Kritika Sharma,&nbsp;N. D. Yash,&nbsp;Mansi Dangi,&nbsp;Maitree Kadamb,&nbsp;Aparna shrivastava,&nbsp;J. Senthil Kumaran,&nbsp;Sakshi Yadav,&nbsp;Monika Jain,&nbsp;Amit Kumar Singh,&nbsp;Jayaraman Muthukumaran","doi":"10.1007/s00894-026-06960-9","DOIUrl":"10.1007/s00894-026-06960-9","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Context&lt;/h3&gt;&lt;p&gt;Dysregulation of apoptosis mediated by antiapoptotic Bcl-2 family proteins contributes significantly to cancer progression and treatment resistance. Although the BH3 mimetic venetoclax has demonstrated remarkable clinical efficacy, the emergence of resistance-associated mechanisms has created a need for alternative Bcl-2-targeting scaffolds. Benzopyran derivatives, including 4&lt;i&gt;H&lt;/i&gt;-chromene and chromone derivatives, represent a structurally diverse class of compounds with reported anticancer and apoptosis-modulating activities; however, their interaction landscape with Bcl-2 remains insufficiently explored. In the present study, a curated library of 356 benzopyran family compounds was investigated against Bcl-2 to identify potential lead candidates. Three compounds, PM28524659, PM31145889, and PM34262894, exhibited favorable binding characteristics relative to the reference chromene-derived Bcl-2 inhibitor HA14-1. Binding mode analysis indicated occupancy of the BH3-binding groove, with interactions involving ASP49, ARG53, and TYR148 residues. Molecular similarity, scaffold, and pharmacophore analyses revealed preservation of key target recognition features despite low overall structural similarity to HA14-1. Based on their physicochemical, pharmacokinetic, and molecular descriptor profiles, PM28524659 and PM31145889 were selected for further investigation through long-timescale molecular dynamics simulations. Both complexes remained stable throughout the 500-ns MD simulation period and maintained favorable interactions with the binding pocket while preserving the overall structural integrity of Bcl-2 protein. Although the identified compounds exhibited lower predicted binding affinity than venetoclax, their favorable ligand efficiency, relatively simple molecular architecture, and scope for structural optimization support their further evaluation as Bcl-2-targeting scaffolds for apoptosis-directed anticancer drug discovery.&lt;/p&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;A dataset comprising 356 curated benzopyran family compounds was subjected to virtual screening against Bcl-2 (PDB ID: 6O0K) using AutoDock Vina. Protein–ligand interactions were analyzed using Discovery Studio Visualizer and PyMOL. Molecular similarity, scaffold, and pharmacophore analyses were performed using two-dimensional and three-dimensional descriptor-based approaches. Drug-likeness, physicochemical properties, pharmacokinetic parameters, and toxicity profiles were assessed using SwissADME, ProTox-3, and related cheminformatics tools. The selected protein–ligand complexes were further investigated by 500-ns molecular dynamics simulations using GROMACS 2025.3 and the CHARMM36 force field in an explicit solvent environment employing the CHARMM-modified TIP3P water model. Trajectory analyses included root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (&lt;i&gt;R&lt;/i&gt;&lt;sub&gt;g&lt;/sub&gt;), solvent-accessible surface area (SASA), intermolecular hydro","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the antioxidant potential of thiamazole through the HAT, SETPT, and SPLET antiradical mechanisms of hydrogen abstraction using DFT","authors":"Mahmoud Mirzaei,&nbsp;Hadil Faris Alotaibi,&nbsp;Aziz Kubaev","doi":"10.1007/s00894-026-06971-6","DOIUrl":"10.1007/s00894-026-06971-6","url":null,"abstract":"<div><h3>Context</h3><p>Regarding the importance of employing antioxidants for dealing with the wild free radicals in the human body system, we performed this work for exploring a potential antioxidant compound. The major HAT, SETPT, and SPLET antiradical mechanisms for exploring the antioxidant potential of thiamazole were assessed through the hydrogen abstraction from all hydrogen involving atomic sites of chemical structure. The hydrogen abstraction from the C–H, N–H, and S–H groups of thio and thiol tautomeric conformers of thiamazole (T1 and T2) were considered to assess the antiradical mechanisms. The evaluated results demonstrated the suitability of models for the hydrogen abstraction from the N–H and S–H groups rather than the C–H group but with a limitation of targeting S–H group in the case of supplying an enthalpic barrier of T2 formation. Additionally, the HAT mechanism was found as the best pathway of antiradical mechanism for thiamazole and the SETPT and SPLET mechanisms were placed in the next levels of preference. As a remarkable conclusion, thiamazole could be considered for working as a potential antioxidant regarding the meaningful thermochemical features of antiradical mechanism; however, the kinetic features and clinical limitations are still major concerns to be resolved before proposing for a real practical use.</p><h3>Methods</h3><p>Density functional theory (DFT) calculations were performed using the B3LYP functional and the 6-311 +  + G** and 6-311G** basis sets as implemented in the Gaussian 16 software.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the catalytic performance of theoretical design series single-atom transition metal-doped TM-N3S-PC catalysts for electrochemical synthesis of NH3","authors":"Yajie Pan,&nbsp;Xiaojuan Liang,&nbsp;Mian Yang,&nbsp;Xiangyang Liu,&nbsp;Jiajia Yang,&nbsp;Donghui Xu,&nbsp;Liuxia Liu","doi":"10.1007/s00894-026-06969-0","DOIUrl":"10.1007/s00894-026-06969-0","url":null,"abstract":"<div><h3>Context</h3><p>Electrocatalytic nitrogen reduction to ammonia is a sustainable alternative to the energy-intensive Haber–Bosch process. Herein, density functional theory calculations were used to systematically evaluate the N₂ reduction reaction over 23 TM-N₃S-PC catalysts, assessing adsorption configurations, energies, and charge transfer. Based on free energy changes of the first and last protonation steps and the competing H adsorption, five active catalysts (V, Cr, Mn, W, Nb) were selected. Detailed mechanism analyses reveal that V and Nb favor the Consecutive pathway, while Cr, Mn, and W proceed via the Distal pathway. Cr-N₃S-PC exhibits the highest limiting potential. The Nb‑N₃S‑PC and W‑N₃S‑PC catalysts hold potential for ENRR and can outcompete the HER. This work provides theoretical insights for the rational design of N₂ to NH₃ electrocatalysts.</p><h3>Methods</h3><p>The configuration, adsorption energy and charge transfer were investigated using the VASP software. The PBE generalized gradient approximation was employed, and the Grimme’s DFT-D3 method was applied in all calculations to incorporate van der Waals corrections. AIMD simulations based on the NVT ensemble were performed to predict the stability of the catalysts. AIMD simulations were conducted using the CP2K 2.3.1 package.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the variational quantum eigensolver (VQE) for bond dissociation of H(_{2}), H({_3^+}), and CH(_{5}^{+})","authors":"Amanda Marques de Lima,&nbsp;Eivson Darlivam Rodrigues de Aguiar Silva,&nbsp;Erico Souza Teixeira,&nbsp;Ricardo Luiz Longo","doi":"10.1007/s00894-026-06951-w","DOIUrl":"10.1007/s00894-026-06951-w","url":null,"abstract":"<div><h3>Context</h3><p>The variational quantum eigensolver (VQE) is a quantum-classical algorithm for estimating molecular ground-state energies. However, the accuracy depends on the choice of <i>ansatz</i>, active space, and initial variational parameters. Hence, it is relevant to perform assessments of VQE. The dissociation profiles of H<span>(_2)</span>, H<span>(_3^+)</span>, and CH<span>(_5^+)</span> were chosen for these assessments. For H<span>(_2)</span> and H<span>(_3^+)</span>, the UCCSD, GateFabric, and <i>k</i>-UpCCGSD <i>ansätze</i> reproduced the dissociation profiles with high accuracy. For CH<span>(_5^+)</span>, GateFabric and <i>k</i>-UpCCGSD provided the best compromise between accuracy and scalability. Hardware-efficient <i>ansätze</i> (HEA), particularly HEA-A and HEA-B, produced significant deviations from the reference energies. The results also demonstrate that larger numbers of parameters or logic gates do not necessarily improve VQE performance. Furthermore, some <i>ansätze</i>, especially GRSD and EHA, showed sensitivity to the initialization of the parameters.</p><h3>Methods</h3><p>Reference geometries and energies were obtained at the CISD/STO-3 G level using Gaussian 09. VQE simulations were performed with the PennyLane library employing the Jordan-Wigner mapping. The <i>ansätze</i> evaluated were UCCSD, <i>k</i>-UpCCGSD, GateFabric, GRSD, HEA-A, HEA-B, HEA-C, and Entanglement-variational Hardware-efficient <i>Ansatz</i> (EHA). Dissociation profiles were generated by varying interatomic distances and angular coordinates for H<span>(_2)</span> and H<span>(_3^+)</span>, as well as the C-H<span>(_2)</span> dissociation coordinate for CH<span>(_5^+)</span>. Active-space ranging from 2/2 to 8/8 electrons/orbitals was employed for CH<span>(_5^+)</span>. Variational parameters were optimized using stochastic gradient descent with a convergence threshold of <span>(1 times 10^{-6})</span> E<span>(_h)</span>. The VQE energies were obtained from averages over multiple runs using both zeros and random parameter initializations.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00894-026-06951-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico pathway-based subtractive proteomics for identifying novel drug targets in Candida albicans with structure-guided drug repurposing of aspartate-semialdehyde dehydrogenase inhibitors","authors":"Nithyashree Sriram,&nbsp;Suhadha Parveen Sadiq,&nbsp;Ravikumar Vilwanathan,&nbsp;Thirunavukkarasu Sivaraman,&nbsp;Muthukumar Govindhapriya,&nbsp;Ravi Kumar Trivedi,&nbsp;Muthusamy Sureshan","doi":"10.1007/s00894-026-06962-7","DOIUrl":"10.1007/s00894-026-06962-7","url":null,"abstract":"<div><h3>Context</h3><p><i>Candida albicans</i> is the most common cause of candidemia and is classified as a high-priority pathogen due to its increasing prevalence among fragilised and hospital-based patients. In this study, the subtractive proteomics approach identified 12 key targets involved in vital pathways that play a crucial role in metabolism and regulation, supporting fungal growth, maintaining balance, and enabling pathogenicity. These pathways are essential for the pathogen’s survival and virulence, highlighting them as potential targets for treatments against <i>C. albicans</i> infections. Notably, aspartate-semialdehyde dehydrogenase (ASADH) plays a role in cell wall construction, stress-associated dormancy, and the production of virulence-associated components, which are critical aspects of <i>C. albicans</i> infections. The structure-guided virtual screening identified five potent hits: Acarbose, Iotrolan, Iodixanol, Nystatin, and Ferric derisomaltose, which exhibit better affinity, ranging from −12.25 to −11.90 kcal/mol with <i>Ca</i>ASADH and exhibits stable binding during 500 ns MD simulations, highlighting their potential as lead compounds for anti-<i>C. albicans</i> drug development.</p><h3>Methods</h3><p>Subtractive proteomics pipeline was performed in a standalone Linux environment, and the three-stage Schrödinger’s Glide docking algorithm was used for molecular docking studies. All MD simulations were conducted using GROMACS for 500 ns, and the conformational dynamic stability was examined using RMSD, RMSF, Rg, SASA, PCA, CD-HIT, BLASTp, DrugBank, BlastKOALA, screening, SiteMap, LigPrep, SwissParam, MMPBSA, and CHARMM36 force field.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}