Pub Date : 2025-01-28DOI: 10.1016/j.jmgm.2025.108965
Mubashar Ali , Zunaira Bibi , Tehreem Fatima , Shamsa Kanwal , Houbing Huang , Bakar Bin Khatab Abbasi , Munirah D. Albaqami
This study utilizes first-principles computations to examine the electronic structure, mechanical stability, and optoelectronic responses of arsenic-based (M = Nb, Mo and X = C, N) ceramics. We assessed the stability of these compounds by calculating their formation enthalpies and phonon dispersion curves, which showed that all the compounds we examined are stable and can be synthesized successfully. The robustness of these materials was also analyzed using elastic constants, which further confirmed that the phases are stable and not prone to mechanical instability. Furthermore, the ductility or brittleness of the studied compounds have been assessed by some other mechanical parameters such as Pughs and Poisson ratio, Cauchy pressure, and anisotropy factors. The acquired band structures and density of states demonstrate the metallic nature of all compounds. Additionally, we have explored the several optical attributes compounds in order to understand how these compounds interact with incoming electromagnetic radiation. The remarkable features of compounds are expected to render them suitable for a range of applications.
{"title":"Exploring the electronic structure, mechanical stability and optoelectronic responses of arsenic-based M2AsX (M = Nb, Mo and X = C, N) MAX phase ceramics","authors":"Mubashar Ali , Zunaira Bibi , Tehreem Fatima , Shamsa Kanwal , Houbing Huang , Bakar Bin Khatab Abbasi , Munirah D. Albaqami","doi":"10.1016/j.jmgm.2025.108965","DOIUrl":"10.1016/j.jmgm.2025.108965","url":null,"abstract":"<div><div>This study utilizes first-principles computations to examine the electronic structure, mechanical stability, and optoelectronic responses of arsenic-based <span><math><mrow><msub><mi>M</mi><mn>2</mn></msub><mtext>AsX</mtext></mrow></math></span> (M = Nb, Mo and X = C, N) ceramics. We assessed the stability of these compounds by calculating their formation enthalpies and phonon dispersion curves, which showed that all the compounds we examined are stable and can be synthesized successfully. The robustness of these materials was also analyzed using elastic constants, which further confirmed that the <span><math><mrow><msub><mi>M</mi><mn>2</mn></msub><mtext>AsX</mtext></mrow></math></span> phases are stable and not prone to mechanical instability. Furthermore, the ductility or brittleness of the studied <span><math><mrow><msub><mi>M</mi><mn>2</mn></msub><mtext>AsX</mtext></mrow></math></span> compounds have been assessed by some other mechanical parameters such as Pughs and Poisson ratio, Cauchy pressure, and anisotropy factors. The acquired band structures and density of states demonstrate the metallic nature of all <span><math><mrow><msub><mi>M</mi><mn>2</mn></msub><mtext>AsX</mtext></mrow></math></span> compounds. Additionally, we have explored the several optical attributes <span><math><mrow><msub><mi>M</mi><mn>2</mn></msub><mtext>AsX</mtext></mrow></math></span> compounds in order to understand how these compounds interact with incoming electromagnetic radiation. The remarkable features of <span><math><mrow><msub><mi>M</mi><mn>2</mn></msub><mtext>AsX</mtext></mrow></math></span> compounds are expected to render them suitable for a range of applications.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108965"},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-27DOI: 10.1016/j.jmgm.2025.108966
Feng Gu , Yunqin Xiao , Wenxiu Zou , Shenshen Li , Zhaohui Wang , Qinghua Wang , Jijun Xiao
Molecular Dynamics (MD) simulations were employed to investigate the transport properties of three polyimides comprising various diamines and dianhydrides. The diamines were 2,8-diamine-4,10-dimethyl-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine (TB1) and 3,9-diamine-4,10-dimethyl-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine (TB2); the dianhydrides were 4,4’-(hexafluoroisopropylidene) diphthalic anhydride (6FDA) and 4,4′-oxydiphthalic anhydride (ODPA). And the three polyimides were denoted as p-TB1-6FDA, p-TB1-ODPA and p-TB2-6FDA, respectively. The simulations provided the properties of the bulk polyimides such as glass transition temperature, fractional free volume, and solubility parameter. The results obtained were generally in consistent with experimental findings, which validated the quality of the model construction. Diffusion coefficient of carbon dioxide (CO2) in polyimide membrane was extracted based on mean square displacement analysis. Further research on backbone dihedral distribution and radial distribution function unveiled that Troger (TB1 or TB2) bases exerted strong influence on intra-chain mobility, 6FDA components were evenly distributed in polyimide matrix thus inhibiting inter-chain packing and CO2 molecules in free volume are surrounded by layers formed by Oxygen/Nitrogen atoms.
{"title":"Molecular insight into transport properties of Troger's base based polyimide membrane","authors":"Feng Gu , Yunqin Xiao , Wenxiu Zou , Shenshen Li , Zhaohui Wang , Qinghua Wang , Jijun Xiao","doi":"10.1016/j.jmgm.2025.108966","DOIUrl":"10.1016/j.jmgm.2025.108966","url":null,"abstract":"<div><div>Molecular Dynamics (MD) simulations were employed to investigate the transport properties of three polyimides comprising various diamines and dianhydrides. The diamines were 2,8-diamine-4,10-dimethyl-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine (TB1) and 3,9-diamine-4,10-dimethyl-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine (TB2); the dianhydrides were 4,4’-(hexafluoroisopropylidene) diphthalic anhydride (6FDA) and 4,4′-oxydiphthalic anhydride (ODPA). And the three polyimides were denoted as p-TB1-6FDA, p-TB1-ODPA and p-TB2-6FDA, respectively. The simulations provided the properties of the bulk polyimides such as glass transition temperature, fractional free volume, and solubility parameter. The results obtained were generally in consistent with experimental findings, which validated the quality of the model construction. Diffusion coefficient of carbon dioxide (CO<sub>2</sub>) in polyimide membrane was extracted based on mean square displacement analysis. Further research on backbone dihedral distribution and radial distribution function unveiled that Troger (TB1 or TB2) bases exerted strong influence on intra-chain mobility, 6FDA components were evenly distributed in polyimide matrix thus inhibiting inter-chain packing and CO<sub>2</sub> molecules in free volume are surrounded by layers formed by Oxygen/Nitrogen atoms.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108966"},"PeriodicalIF":2.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Monomer insertion, leading to the formation of an activated monomer complex, is a critical step in cationic ring-opening polymerization (CROP) of cyclic monomers, such as ε-caprolactone (CL). In this study, Density Functional Theory (DFT) calculations were employed to investigate the structural and electronic properties of four activated complexes at two Zr:B ratios (1:2 and 1:1), where Zr is the cationic zirconocene catalyst, Cp₂ZrMe⁺, and B is the borate cocatalyst, [MeB(C6F5)3]‒ or [B(C6F5)4]‒. Steric hindrance at the reactive site was analyzed using topographic steric maps, while inter- and intramolecular interactions of the complex systems were examined through the Quantum Theory of Atoms in Molecules (QTAIM) and non-covalent interaction (NCI) analyses. The 1:2 ratio exhibited significant steric hindrance above and below the monomer plane, restricting access to the Cp₂ZrMe⁺ catalytic site and potentially limiting monomer insertion. In contrast, the 1:1 ratio displayed reduced steric congestion and stronger localized attractive forces at the catalytic site, facilitating better interactions with monomers and solvents. Conceptual DFT descriptors revealed that 1:1 systems had smaller HOMO-LUMO energy gaps, lower hardness, and higher electrophilicity, with 1:1@[B(C₆F₅)₄]⁻ identified as the most reactive complex. QTAIM identified key hydrogen bonding interactions, and the Zr-OCL bonds, distinguishing stability and reactivity across Zr:B ratios. These findings provide valuable insights into the steric and electronic effects on monomer-activated species, enabling the optimization of Zr:B ratios and cocatalyst conditions for improved polymerization efficiency.
{"title":"Exploring the effect of Zr/B ratio on the stability and reactivity of activated ε-caprolactone complexes: A DFT, QTAIM and NCI study","authors":"Wijitra Meelua , Tanchanok Wanjai , Jitrayut Jitonnom","doi":"10.1016/j.jmgm.2025.108960","DOIUrl":"10.1016/j.jmgm.2025.108960","url":null,"abstract":"<div><div>Monomer insertion, leading to the formation of an activated monomer complex, is a critical step in cationic ring-opening polymerization (CROP) of cyclic monomers, such as ε-caprolactone (CL). In this study, Density Functional Theory (DFT) calculations were employed to investigate the structural and electronic properties of four activated complexes at two Zr:B ratios (1:2 and 1:1), where Zr is the cationic zirconocene catalyst, Cp₂ZrMe⁺, and B is the borate cocatalyst, [MeB(C<sub>6</sub>F<sub>5</sub>)<sub>3</sub>]<sup>‒</sup> or [B(C<sub>6</sub>F<sub>5</sub>)<sub>4</sub>]<sup>‒</sup>. Steric hindrance at the reactive site was analyzed using topographic steric maps, while inter- and intramolecular interactions of the complex systems were examined through the Quantum Theory of Atoms in Molecules (QTAIM) and non-covalent interaction (NCI) analyses. The 1:2 ratio exhibited significant steric hindrance above and below the monomer plane, restricting access to the Cp₂ZrMe⁺ catalytic site and potentially limiting monomer insertion. In contrast, the 1:1 ratio displayed reduced steric congestion and stronger localized attractive forces at the catalytic site, facilitating better interactions with monomers and solvents. Conceptual DFT descriptors revealed that 1:1 systems had smaller HOMO-LUMO energy gaps, lower hardness, and higher electrophilicity, with 1:1@[B(C₆F₅)₄]⁻ identified as the most reactive complex. QTAIM identified key hydrogen bonding interactions, and the Zr-O<sub>CL</sub> bonds, distinguishing stability and reactivity across Zr:B ratios. These findings provide valuable insights into the steric and electronic effects on monomer-activated species, enabling the optimization of Zr:B ratios and cocatalyst conditions for improved polymerization efficiency.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108960"},"PeriodicalIF":2.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-24DOI: 10.1016/j.jmgm.2025.108961
Qi Chu , Shuyang Sun , Congcong Li , Ge Qu , Zhoutong Sun
S-adenosylmethionine (SAM)-dependent histamine N-methyltransferase (HNMT) is a crucial enzyme involved in histamine methylation, playing an important role in the epigenetic modification of biology. It entails the addition of methyl groups to histamine molecules, thereby regulating gene expression, cellular signal transduction, and other biological processes. Therefore, gaining a profound understanding of the detailed mechanism underlying HNMT-mediated methylation reactions is instrumental in elucidating the role of histamine methylation in biology. This study employed molecular dynamics (MD) simulations to assess the mechanism of cooperative catalytic reaction between the substrate-binding domain (S domain) and the cofactor-binding domain (C domain) of HNMT. The results indicated that the interplay between the cofactor (SAM) and the C domain was mostly unaltered by substrate Histamine (HSM) binding. Nevertheless, SAM binding could induce conformational changes in the S domain, thus creating a favorable environment for substrate recognition and catalysis. Additionally, key amino acid residues that significantly contributed to substrate binding were identified based on molecular mechanics-generalized Born surface area (MM/GBSA) calculations. These findings could serve as a theoretical basis for the design of potential inhibitors and modulators targeting HNMT.
{"title":"Elucidating the impact of S-adenosylmethionine and histamine binding on N-methyltransferase conformational dynamics: Insights from an in silico study","authors":"Qi Chu , Shuyang Sun , Congcong Li , Ge Qu , Zhoutong Sun","doi":"10.1016/j.jmgm.2025.108961","DOIUrl":"10.1016/j.jmgm.2025.108961","url":null,"abstract":"<div><div>S-adenosylmethionine (SAM)-dependent histamine N-methyltransferase (HNMT) is a crucial enzyme involved in histamine methylation, playing an important role in the epigenetic modification of biology. It entails the addition of methyl groups to histamine molecules, thereby regulating gene expression, cellular signal transduction, and other biological processes. Therefore, gaining a profound understanding of the detailed mechanism underlying HNMT-mediated methylation reactions is instrumental in elucidating the role of histamine methylation in biology. This study employed molecular dynamics (MD) simulations to assess the mechanism of cooperative catalytic reaction between the substrate-binding domain (S domain) and the cofactor-binding domain (C domain) of HNMT. The results indicated that the interplay between the cofactor (SAM) and the C domain was mostly unaltered by substrate Histamine (HSM) binding. Nevertheless, SAM binding could induce conformational changes in the S domain, thus creating a favorable environment for substrate recognition and catalysis. Additionally, key amino acid residues that significantly contributed to substrate binding were identified based on molecular mechanics-generalized Born surface area (MM/GBSA) calculations. These findings could serve as a theoretical basis for the design of potential inhibitors and modulators targeting HNMT.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108961"},"PeriodicalIF":2.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-23DOI: 10.1016/j.jmgm.2025.108959
Sergey L. Khursan , Mikhail Yu. Ovchinnikov , Vladimir T. Varlamov
Gas phase bond dissociation energies (BDE) O-H/N-H in hydroquinone (H2Q), 4-aminophenol (AP), 1,4-phenylenediamine (PDA), 4-hydroxydiphenylamine (HDPA), N,N′-diphenyl-1,4-phenylenediamine (DPPDA) as well as in their phenoxyl/aminyl radicals have been determined using a combined technique of quantum chemical calculation. The technique included a series of DFT (PBE1PBE, TPSSTPSS, M06-2X), ab initio (DLPNO-CCSD(T)) methods with valence 3ξ-basis sets, composite methods of Gaussian family (G4) and Weizmann theory with ab initio Brueckner Doubles (W1BD), as well as reference reactions of different levels of structural similarity. W1BD method was used in combination with isodesmic reactions for BDE estimation (kJ∙mol−1) of compounds with the only aromatic fragment: BDEO-H = 352.3 (H2Q), 340.0 (AP), BDEN-H = 371.2 (AP), 364.1 (PDA) – in molecules; and BDEO-H = 230.4 (H2Q), 228.8 (AP), BDEN-H = 260.0 (AP), 257.1 (PDA) – in corresponding radicals. These values were further applied to estimate the BDEs in HDPA and DPPDA within the homodesmotic reference process and less resource-intensive ab initio methods: BDEO-H = 341.4 (HDPA), BDEN-H = 352.9 (HDPA), 351.3 (DPPDA) for molecules; BDEO-H = 237.4 (HDPA), BDEN-H = 247.4 (HDPA), 252.6 (DPPDA) for radicals. DFT methods give similar results but a slightly larger standard error of calculation. The found values of BDE(O-H/N-H) are compared with literature data; the effect of solvation on BDEs is discussed.
{"title":"O-H/N-H bond dissociation energies in 1,4-hydroquinone, 4-hydroxydiphenylamine, N,N′-diphenyl-1,4-phenylenediamine, and their phenoxyl and aminyl radicals","authors":"Sergey L. Khursan , Mikhail Yu. Ovchinnikov , Vladimir T. Varlamov","doi":"10.1016/j.jmgm.2025.108959","DOIUrl":"10.1016/j.jmgm.2025.108959","url":null,"abstract":"<div><div>Gas phase bond dissociation energies (<em>BDE</em>) O-H/N-H in hydroquinone (<strong>H</strong><sub><strong>2</strong></sub><strong>Q</strong>), 4-aminophenol (<strong>AP</strong>), 1,4-phenylenediamine (<strong>PDA</strong>), 4-hydroxydiphenylamine (<strong>HDPA</strong>), N,N′-diphenyl-1,4-phenylenediamine (<strong>DPPDA</strong>) as well as in their phenoxyl/aminyl radicals have been determined using a combined technique of quantum chemical calculation. The technique included a series of DFT (PBE1PBE, TPSSTPSS, M06-2X), <em>ab initio</em> (DLPNO-CCSD(T)) methods with valence 3ξ-basis sets, composite methods of Gaussian family (G4) and Weizmann theory with <em>ab initio</em> Brueckner Doubles (W1BD), as well as reference reactions of different levels of structural similarity. W1BD method was used in combination with isodesmic reactions for <em>BDE</em> estimation (kJ∙mol<sup>−1</sup>) of compounds with the only aromatic fragment: <em>BDE</em><sub>O-H</sub> = 352.3 (<strong>H</strong><sub><strong>2</strong></sub><strong>Q</strong>), 340.0 (<strong>AP</strong>), <em>BDE</em><sub>N-H</sub> = 371.2 (<strong>AP</strong>), 364.1 (<strong>PDA</strong>) – in molecules; and <em>BDE</em><sub>O-H</sub> = 230.4 (<strong>H</strong><sub><strong>2</strong></sub><strong>Q</strong>), 228.8 (<strong>AP</strong>), <em>BDE</em><sub>N-H</sub> = 260.0 (<strong>AP</strong>), 257.1 (<strong>PDA</strong>) – in corresponding radicals. These values were further applied to estimate the <em>BDE</em>s in <strong>HDPA</strong> and <strong>DPPDA</strong> within the homodesmotic reference process and less resource-intensive <em>ab initio</em> methods: <em>BDE</em><sub>O-H</sub> = 341.4 (<strong>HDPA</strong>), <em>BDE</em><sub>N-H</sub> = 352.9 (<strong>HDPA</strong>), 351.3 (<strong>DPPDA</strong>) for molecules; <em>BDE</em><sub>O-H</sub> = 237.4 (<strong>HDPA</strong>), <em>BDE</em><sub>N-H</sub> = 247.4 (<strong>HDPA</strong>), 252.6 (<strong>DPPDA</strong>) for radicals. DFT methods give similar results but a slightly larger standard error of calculation. The found values of <em>BDE</em>(O-H/N-H) are compared with literature data; the effect of solvation on <em>BDE</em>s is discussed.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108959"},"PeriodicalIF":2.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-22DOI: 10.1016/j.jmgm.2025.108958
Chou-Yi Hsu , Mohammed Hashim Mohammed , Dharmesh Sur , Suhas Ballal , Abhayveer Singh , T. Krithiga , Subhashree Ray , Hayder Ridha-Salman , Abdulrahman A. Almehizia
Investigating effective nanomaterials for the detection of hydroxyurea anticancer drugs is essential for promoting human health and safeguarding environmental integrity. This research utilized first-principles estimations for examining the adhesion and electronic characteristics of hydroxyurea (HU) on both pristine and Si-decorated innovative two-dimensional boron nitride allotrope, known as Irida analogous (Ir-BNNS). Analyzing the adsorption energy revealed that the HU molecule has a significant interaction (Ead = −1.27 eV) with the Si@Ir-BNNS, whereas it has weak interaction P-Ir-BN. Moreover, the analysis of the electron density distributions was conducted to investigate the microcosmic interaction mechanism between HU and Ir-BNNS. The Si@Ir-BNNS was highly sensitive to HU due to the observable alterations in the electrical conductance and magnetism. At ambient temperature, the Si@Ir-BNNS had a recovery time of 5.96 ms towards HU molecules. The DFT estimations can be conducive to exploring the applications of Si@Ir-BNNS in effectively sensing HU.
{"title":"A DFT study of pure and Si-decorated boron nitride allotrope Irida monolayer as an effective sensor for hydroxyurea drug","authors":"Chou-Yi Hsu , Mohammed Hashim Mohammed , Dharmesh Sur , Suhas Ballal , Abhayveer Singh , T. Krithiga , Subhashree Ray , Hayder Ridha-Salman , Abdulrahman A. Almehizia","doi":"10.1016/j.jmgm.2025.108958","DOIUrl":"10.1016/j.jmgm.2025.108958","url":null,"abstract":"<div><div>Investigating effective nanomaterials for the detection of hydroxyurea anticancer drugs is essential for promoting human health and safeguarding environmental integrity. This research utilized first-principles estimations for examining the adhesion and electronic characteristics of hydroxyurea (HU) on both pristine and Si-decorated innovative two-dimensional boron nitride allotrope, known as Irida analogous (Ir-BNNS). Analyzing the adsorption energy revealed that the HU molecule has a significant interaction (E<sub>ad</sub> = −1.27 eV) with the Si@Ir-BNNS, whereas it has weak interaction P-Ir-BN. Moreover, the analysis of the electron density distributions was conducted to investigate the microcosmic interaction mechanism between HU and Ir-BNNS. The Si@Ir-BNNS was highly sensitive to HU due to the observable alterations in the electrical conductance and magnetism. At ambient temperature, the Si@Ir-BNNS had a recovery time of 5.96 ms towards HU molecules. The DFT estimations can be conducive to exploring the applications of Si@Ir-BNNS in effectively sensing HU.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108958"},"PeriodicalIF":2.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-20DOI: 10.1016/j.jmgm.2025.108956
Sukriti Singh , Jyotsna Agarwal , Anupam Das , Mala Trivedi , Kshatresh D. Dubey , K.V. Athish Pranav , Manish Dwivedi
The Acinetobacter baumannii is a member of the "ESKAPE" bacteria responsible for many serious multidrug-resistant (MDR) illnesses. This bacteria swiftly adapts to environmental cues leading to the emergence of multidrug-resistant variants, particularly in hospital/medical settings. In this work, we have demonstrated the outer membrane protein 33-36 (Omp33-36) porin as a potential therapeutic target in A. baumannii and the regulatory potential of phytocompounds using an in-silico drug screening approach. Omp33-36 protein receptor was retrieved from the protein data bank and characterized as a receptor protein. The possible compounds (ligands) from three plants namely Andrographis paniculata, Cascabela thevetia, and Prosopis cineraria, were evaluated for their potential against bacterial infections based on prior investigations and selected for further analysis. Initially, seventy potential phytocompounds were identified and retrieved from IMPPAT database, followed by Physio-chemical characterizations and toxicity assessment using swissADME and ProTox server respectively. 15 compounds have shown significant drug-likeliness and were implemented for their interaction analysis with Omp33-36 using Autodock Vina. The docking study presented seven compounds with the best binding affinities, ranging from −7.2 kcal/mol to −7.9 kcal/mol and further, based on the potential of these compounds, 4 phytocompounds were introduced for molecular dynamic simulation for 200ns. During MD simulation, compounds Prosogerin, Quercitin and Tamarixetin have shown a substantial affinity for the Omp33-36 protein and binding energy ranging from −18 to −33 kcal/mol. Overall, the analysis depicted the two compounds, Quercitin and Tamarixetin, with the most consistent interactions and indicated promise as drug leads in regulating A. baumannii infection. However, in-vitro and in-vivo experimental validation are required to propose the selected phytomolecules as a therapeutic lead against A. baumannii.
{"title":"Leveraging molecular dynamics, physicochemical, and structural analysis to explore OMP33-36 protein as a drug target in Acinetobacter baumannii: An approach against nosocomial infection","authors":"Sukriti Singh , Jyotsna Agarwal , Anupam Das , Mala Trivedi , Kshatresh D. Dubey , K.V. Athish Pranav , Manish Dwivedi","doi":"10.1016/j.jmgm.2025.108956","DOIUrl":"10.1016/j.jmgm.2025.108956","url":null,"abstract":"<div><div>The <em>Acinetobacter baumannii</em> is a member of the \"ESKAPE\" bacteria responsible for many serious multidrug-resistant (MDR) illnesses. This bacteria swiftly adapts to environmental cues leading to the emergence of multidrug-resistant variants, particularly in hospital/medical settings. In this work, we have demonstrated the outer membrane protein 33-36 (Omp33-36) porin as a potential therapeutic target in <em>A. baumannii</em> and the regulatory potential of phytocompounds using an <em>in-silico</em> drug screening approach. Omp33-36 protein receptor was retrieved from the protein data bank and characterized as a receptor protein. The possible compounds (ligands) from three plants namely <em>Andrographis paniculata, Cascabela thevetia</em>, and <em>Prosopis cineraria</em>, were evaluated for their potential against bacterial infections based on prior investigations and selected for further analysis. Initially, seventy potential phytocompounds were identified and retrieved from IMPPAT database, followed by Physio-chemical characterizations and toxicity assessment using swissADME and ProTox server respectively. 15 compounds have shown significant drug-likeliness and were implemented for their interaction analysis with Omp33-36 using Autodock Vina. The docking study presented seven compounds with the best binding affinities, ranging from −7.2 kcal/mol to −7.9 kcal/mol and further, based on the potential of these compounds, 4 phytocompounds were introduced for molecular dynamic simulation for 200ns. During MD simulation, compounds Prosogerin, Quercitin and Tamarixetin have shown a substantial affinity for the Omp33-36 protein and binding energy ranging from −18 to −33 kcal/mol. Overall, the analysis depicted the two compounds, Quercitin and Tamarixetin, with the most consistent interactions and indicated promise as drug leads in regulating <em>A. baumannii</em> infection. However, <em>in-vitro</em> and <em>in-vivo</em> experimental validation are required to propose the selected phytomolecules as a therapeutic lead against <em>A. baumannii</em>.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108956"},"PeriodicalIF":2.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Interleukin (IL) 37 is an anti-inflammatory cytokine belonging to the IL1 protein family. Owing to its pivotal role in modulating immune responses, elucidating the IL37 complex structures holds substantial therapeutic promise for various autoimmune disorders and cancers. However, none of the structures of IL37 complexes have been experimentally characterized. This computational study aims to address this gap through molecular modeling and classical molecular dynamics simulations. We modeled all protein–protein complexes of IL37 using a range of methods from homology modeling to AlphaFold2 multimer predictions. Models that successfully recapitulated experimental features underwent further analysis through molecular dynamics simulations. As positive controls, binary and ternary complexes of IL18 from PDB were included for comparison. Several key findings emerged from the comparative analysis of IL37 and IL18 complexes. IL37 complexes exhibited higher mobility than the IL18 complexes. Simulations of the IL37-IL18R complex revealed altered receptor conformations capable of accommodating a dimeric IL37, with the N-terminal loop of IL37 contributing significantly to complex mobility. Additionally, the glycosyl chain on N297 of IL18R, which contours one edge of the cytokine binding surface, acted as a steric block against the N-terminal loop of IL37. Further, investigations into interactions between IL37 and IL18BP suggested that a binding mode homologous to IL18 was unstable for IL37, indicating an alternative binding mechanism. Altogether, this study accesses to the structure and dynamics of IL37 complexes, revealing the structural underpinnings of the IL37’s modulatory effect on the IL18 signaling pathway.
{"title":"Computational modeling of the anti-inflammatory complexes of IL37","authors":"Inci Sardag , Zeynep Sevval Duvenci , Serkan Belkaya , Emel Timucin","doi":"10.1016/j.jmgm.2025.108952","DOIUrl":"10.1016/j.jmgm.2025.108952","url":null,"abstract":"<div><div>Interleukin (IL) 37 is an anti-inflammatory cytokine belonging to the IL1 protein family. Owing to its pivotal role in modulating immune responses, elucidating the IL37 complex structures holds substantial therapeutic promise for various autoimmune disorders and cancers. However, none of the structures of IL37 complexes have been experimentally characterized. This computational study aims to address this gap through molecular modeling and classical molecular dynamics simulations. We modeled all protein–protein complexes of IL37 using a range of methods from homology modeling to AlphaFold2 multimer predictions. Models that successfully recapitulated experimental features underwent further analysis through molecular dynamics simulations. As positive controls, binary and ternary complexes of IL18 from PDB were included for comparison. Several key findings emerged from the comparative analysis of IL37 and IL18 complexes. IL37 complexes exhibited higher mobility than the IL18 complexes. Simulations of the IL37-IL18R<span><math><mi>α</mi></math></span> complex revealed altered receptor conformations capable of accommodating a dimeric IL37, with the N-terminal loop of IL37 contributing significantly to complex mobility. Additionally, the glycosyl chain on N297 of IL18R<span><math><mi>α</mi></math></span>, which contours one edge of the cytokine binding surface, acted as a steric block against the N-terminal loop of IL37. Further, investigations into interactions between IL37 and IL18BP suggested that a binding mode homologous to IL18 was unstable for IL37, indicating an alternative binding mechanism. Altogether, this study accesses to the structure and dynamics of IL37 complexes, revealing the structural underpinnings of the IL37’s modulatory effect on the IL18 signaling pathway.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108952"},"PeriodicalIF":2.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-18DOI: 10.1016/j.jmgm.2025.108955
M. Perić, Z. Milanović, M. Mirković, M. Radović, A. Vukadinović
Technetium-99m plays a pivotal role in nuclear medicine, offering unique IMAGING capabilities due to its favorable physical and chemical properties. This study investigates the redox behavior and electronic structures of three representative Tc(V) oxo complexes, [TcO(HMPAO)], [TcO(Bicisate)], and [TcO(DMSA)2]-, using computational techniques. Employing relativistic density functional theory with the Zero-Order Regular Approximation (ZORA), we analyze singlet-triplet energy gaps, Gibbs free energy changes, and redox potentials in neutral and acidic environments. The results highlight the significant influence of co-ligands on the electronic stabilization of complexes and their tendencies toward reduction and protonation. The findings also elucidate the role of Jahn-Teller distortions in shaping the redox properties of the studied complexes. Redox potential trends indicate enhanced reducibility in complexes with sulfur-based ligands, impacting their clinical utility. This study provides valuable insights into the design and optimization of technetium-based radiopharmaceuticals, emphasizing their stability and behavior under physiological conditions.
{"title":"Computational insights into the redox properties and electronic structures of [Tc=O]3+ complexes: Implications for 99mTc-radiopharmaceuticals","authors":"M. Perić, Z. Milanović, M. Mirković, M. Radović, A. Vukadinović","doi":"10.1016/j.jmgm.2025.108955","DOIUrl":"10.1016/j.jmgm.2025.108955","url":null,"abstract":"<div><div>Technetium-99m plays a pivotal role in nuclear medicine, offering unique IMAGING capabilities due to its favorable physical and chemical properties. This study investigates the redox behavior and electronic structures of three representative Tc(V) oxo complexes, [TcO(HMPAO)], [TcO(Bicisate)], and [TcO(DMSA)<sub>2</sub>]<sup>-</sup>, using computational techniques. Employing relativistic density functional theory with the Zero-Order Regular Approximation (ZORA), we analyze singlet-triplet energy gaps, Gibbs free energy changes, and redox potentials in neutral and acidic environments. The results highlight the significant influence of co-ligands on the electronic stabilization of complexes and their tendencies toward reduction and protonation. The findings also elucidate the role of Jahn-Teller distortions in shaping the redox properties of the studied complexes. Redox potential trends indicate enhanced reducibility in complexes with sulfur-based ligands, impacting their clinical utility. This study provides valuable insights into the design and optimization of technetium-based radiopharmaceuticals, emphasizing their stability and behavior under physiological conditions.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108955"},"PeriodicalIF":2.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-18DOI: 10.1016/j.jmgm.2025.108957
Pradeepa A , Arathi P
Topological indices are numerical invariants that provide key insights into the structural properties of molecular graphs and are crucial in predicting physio-chemical and biological activities. This paper applies established computational methodologies for analyzing benzenoid networks and their application to polycyclic aromatic hydrocarbons (PAHs) through degree-based topological indices computed via M-polynomial and NM-polynomial approaches. By examining tessellations, including linear chain, hexagonal, rhomboidal, and triangular configurations alongside their line graphs, this work highlights the influence of molecular topology on biological activity. Notably, the line graph of hexagonal tessellations resembling Kagome structures exhibits the highest potential bioactivity, revealing additional connectivity patterns that offer a structured framework for early-stage drug discovery and potentially enhance the understanding of molecular interactions. These findings underscore the value of topological indices in identifying key structural features, reducing attrition rates in drug development, and improving screening technologies, contributing to efficient drug design.
{"title":"On topological characterizations and computational analysis of benzenoid networks for drug discovery and development","authors":"Pradeepa A , Arathi P","doi":"10.1016/j.jmgm.2025.108957","DOIUrl":"10.1016/j.jmgm.2025.108957","url":null,"abstract":"<div><div>Topological indices are numerical invariants that provide key insights into the structural properties of molecular graphs and are crucial in predicting physio-chemical and biological activities. This paper applies established computational methodologies for analyzing benzenoid networks and their application to polycyclic aromatic hydrocarbons (PAHs) through degree-based topological indices computed via M-polynomial and NM-polynomial approaches. By examining tessellations, including linear chain, hexagonal, rhomboidal, and triangular configurations alongside their line graphs, this work highlights the influence of molecular topology on biological activity. Notably, the line graph of hexagonal tessellations resembling Kagome structures exhibits the highest potential bioactivity, revealing additional connectivity patterns that offer a structured framework for early-stage drug discovery and potentially enhance the understanding of molecular interactions. These findings underscore the value of topological indices in identifying key structural features, reducing attrition rates in drug development, and improving screening technologies, contributing to efficient drug design.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108957"},"PeriodicalIF":2.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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