Journal of molecular graphics & modelling最新文献

{"title":"Computational insights into the redox properties and electronic structures of [Tc=O]3+ complexes: Implications for 99mTc-radiopharmaceuticals","authors":"M. Perić,&nbsp;Z. Milanović,&nbsp;M. Mirković,&nbsp;M. Radović,&nbsp;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)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.</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}

{"title":"On topological characterizations and computational analysis of benzenoid networks for drug discovery and development","authors":"Pradeepa A ,&nbsp;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}

{"title":"Computer-aided drug design approaches for the identification of potent inhibitors targeting elongation factor G of Mycobacterium tuberculosis","authors":"Mushtaq Ahmad Wani,&nbsp;Aritra Banerjee,&nbsp;Prabha Garg","doi":"10.1016/j.jmgm.2025.108954","DOIUrl":"10.1016/j.jmgm.2025.108954","url":null,"abstract":"<div><div>Elongation factor G (EF-G) is essential for protein synthesis in <em>Mycobacterium tuberculosis</em> (Mtb), positioning it as a promising target for anti-tubercular drug development. This study employs Structure-Based Drug Design (SBDD) to identify potential small molecule inhibitors that specifically target EF-G. Initially, binding hotspots on EF-G were pinpointed, and the binding modes of various compounds were analyzed. Through protein-protein interaction studies, several promising candidates were validated. Virtual screening and molecular docking techniques were utilized to evaluate the binding affinities and interactions of 20 candidate molecules with Mtb EF-G. Additionally, toxicity profiles of these compounds were assessed using predictive models, which indicated non-carcinogenic properties. To further refine the selection process, Support Vector Machine (SVM) and Random Forest models were applied to predict cell wall permeability. Notably, Asinex (8853) and Asinex (102619) emerged as top candidates, boasting high probability scores for effective permeability. Molecular docking and molecular dynamics (MD) simulations revealed that Asinex (8853), Asinex (102619), and Otava (79226) exhibited strong binding affinities and favorable conformations within the active site of Mtb EF-G. These findings suggest that these compounds have significant potential as inhibitors, warranting further investigation into their efficacy as novel anti-tubercular agents. Overall, this study emphasizes the value of Structure-Based Drug Design in identifying promising therapeutic candidates against tuberculosis by targeting essential bacterial factors like EF-G.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108954"},"PeriodicalIF":2.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039622","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}

{"title":"DFT study of GaAs quantum dot and 5CB liquid crystal molecule interaction","authors":"L.S. Elbakyan ,&nbsp;D.B. Hayrapetyan ,&nbsp;P.A. Mantashyan","doi":"10.1016/j.jmgm.2025.108953","DOIUrl":"10.1016/j.jmgm.2025.108953","url":null,"abstract":"<div><div>Liquid crystals (LC) are widely used in various optical devices due to their birefringence, dielectric anisotropy, and responsive behavior to external fields. Enhancing the properties of existing LCs through doping with nanoparticles, including semiconductor quantum dots, offers a promising route for improving their performance. Among various nanoparticles, QDs stand out for their high charge mobility, sensitivity in the near-infrared spectral region, and cost-effectiveness. These attributes make them ideal candidates for integration with LCs. While liquid crystalline behavior arises from the collective ordering of molecules, the microscopic interactions between QDs and LC molecules remain an intriguing area of study to understand the underlying quantum-level mechanisms.</div><div>In this study, we employ Density Functional Theory to investigate the interaction between GaAs quantum dot and a 5CB molecule. The 5CB molecule and Ga atoms were brought together gradually, and the corresponding changes in interaction energy and electron density distributions were calculated. The energy profiles reveal a clear distance-dependent interaction, with a minimum observed at 2.1 Å, indicating the formation of stable complexes. While the BVP86 functional slightly overestimated the interaction energy, the B3LYP functional produced more accurate results, confirming the feasibility of stable quantum dot – 5CB molecule complexes.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108953"},"PeriodicalIF":2.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006902","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}

{"title":"Glipizide inhibits the glycation of alpha-crystallin: A combined in vitro and in silico approach in retinopathy management","authors":"Ting Li ,&nbsp;Bo Ma ,&nbsp;Li Zhang ,&nbsp;Mingli Wang","doi":"10.1016/j.jmgm.2025.108950","DOIUrl":"10.1016/j.jmgm.2025.108950","url":null,"abstract":"<div><div>In human eye, structural proteins, known as crystallins, play a crucial role in maintaining the eye's refractive index. These crystallins constitute majority of the total soluble proteins found in the eye lens. Among them, α-crystallins (α-CR) is one of the major components. Under hyperglycaemic conditions, crystallins become susceptible to glycation that ultimately leads to advanced glycation endproducts (AGEs) formation. Glipizide is a well-known oral medication used in controlling levels of blood sugar, this drug stimulates the insulin release from pancreas. However, this drug has not been thoroughly investigated for its impact on α-CR glycation. In this study, we explored glipizide's protective role against glucose-induced α-CR glycation. Remarkably, glipizide effectively inhibited the formation of early glycation products, ultimately reducing AGEs formation. Additionally, glipizide provides protection against modifications of free lysine residues and lowered the carbonyl content. To gain deeper insights into mechanism of inhibition, we turn to binding studies and bioinformatics. Glipizide formed stable complex with α-CR with values of Gibbs energy ranging from −5.848 to −6.695 kcal/mol. Molecular docking revealed the binding energy as −6.5 kcal/mol and lysine residues emerged as a prominent among the key interacting residues. Notably, glipizide appears to mask lysine residues, thereby contributing to the inhibition of α-CR glycation. Furthermore, analysis of molecular simulation data reinforces the stability of this complex. Consequently, the stable α-CR-glipizide complex may prevent glucose from binding to α-CR. Overall, glipizide holds promise as a preventive measure against glycation of eye lens proteins, potentially benefiting in diabetic retinopathy.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108950"},"PeriodicalIF":2.7,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983837","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}

{"title":"Borophene based quasi planar nanocluster for ethanol, isobutanol, and acetone sensing: A first principle study","authors":"Nima Ajalli ,&nbsp;Forough Rezaie ,&nbsp;Saeedeh Kamalinahad ,&nbsp;Jafar Azamat","doi":"10.1016/j.jmgm.2025.108951","DOIUrl":"10.1016/j.jmgm.2025.108951","url":null,"abstract":"<div><div>In this study, the need for efficient detection of volatile organic compounds (VOCs) in environmental monitoring, industrial safety, is addressed by investigating borophene-based B36 nanoclusters as gas sensors. Density functional theory (DFT) calculations were employed to examine the adsorption behavior of ethanol, isobutanol, and acetone on B₃₆ surfaces, with a focus on vibrational modes, reactivity, and adsorption energies. It was found that acetone exhibits the strongest interaction with pristine B₃₆, indicating its potential for robust sensing applications. To further enhance sensor performance, the effects of doping B₃₆ with nickel (Ni) and iron (Fe) atoms were explored. The electronic structure was significantly modified in Fe@B₃₆, showing strong chemisorption properties, while Ni@B₃₆ showed less impact, serving as a counterexample. Additionally, conductivity, recovery time, and global reactivity parameters were analyzed, providing insights into the sensor's functionality. It is suggested that B₃₆ nanoclusters, particularly Fe-doped systems, offer promising prospects for future gas sensor development and VOC detection.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108951"},"PeriodicalIF":2.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983835","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}

{"title":"Nanoring interactions with bio-relevant molecule: A quantum chemical approach to C18 and B9N9 systems","authors":"A.K. Vishwkarma ,&nbsp;T. Yadav ,&nbsp;E. Shakerzadeh ,&nbsp;S. Goswami ,&nbsp;S. Garai ,&nbsp;V. Vetrivelan ,&nbsp;J. Adam ,&nbsp;A. Pathak","doi":"10.1016/j.jmgm.2025.108949","DOIUrl":"10.1016/j.jmgm.2025.108949","url":null,"abstract":"<div><div>This study investigates the interaction of a synthetic bio-relevant molecule with C₁₈ and B₉N₉ nanorings, exploring their potential applications in sensing and drug delivery. Employing Density Functional Theory (DFT) at the ωB97XD level with the 6-31G(d,p) basis set, we computed the adsorption and electronic properties of the resulting nanocomplexes. A total of ten distinct configurations were identified for the interactions, with adsorption energies ranging from −6.75 to −12.62 kcal/mol for the C₁₈@target molecule and −9.01 to −18.46 kcal/mol for the B₉N₉@target molecule. Notably, alterations in the energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) upon interaction suggest an enhancement in electrical conductivity. The effect of aqueous media was also examined, revealing an increase of approximately 2.0 Debye in the dipole moments of the most stable nanocomplexes. Additional analyses, including reduced density gradient (RDG), UV–Vis spectroscopy, and Quantum Theory of Atoms in Molecules (QTAIM), were conducted in both gas and aqueous phases. Our findings indicate that C₁₈ and B₉N₉ nanorings exhibit significant promise as candidates for drug delivery and sensing applications, particularly due to their enhanced electronic properties upon interaction with the bio-relevant molecule.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108949"},"PeriodicalIF":2.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978753","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}

{"title":"In silico evaluation of bisphosphonates identifies leading candidates for SARS-CoV-2 RdRp inhibition","authors":"Mohammed Muzaffar-Ur-Rehman ,&nbsp;Kishor Suryakant Chougule ,&nbsp;Ala Chandu ,&nbsp;Pranali Vijaykumar Kuthe ,&nbsp;Mohit Garg ,&nbsp;Murugesan Sankaranarayanan ,&nbsp;Seshadri S. Vasan","doi":"10.1016/j.jmgm.2024.108939","DOIUrl":"10.1016/j.jmgm.2024.108939","url":null,"abstract":"<div><div>The novel coronavirus disease (COVID-19) pandemic has resulted in 777 million confirmed cases and over 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Post Acute Sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various <em>in silico</em>, <em>in vitro</em> and <em>ex vivo</em> models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and <em>in silico</em> studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. In this study, we have investigated all bisphosphonates (BPs) on the ChEMBL database which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an <em>in silico</em> mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies in Japan with minodronate could be valuable.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108939"},"PeriodicalIF":2.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular dynamics simulations to decipher the hotspots at the allosteric site of human 5-lipoxygenase","authors":"Sahanawaz Parvez ,&nbsp;Kallepalli Sarala Bhavani ,&nbsp;Chandaluri Chanchayya Gupta ,&nbsp;Oliver Werz ,&nbsp;Polamarasetty Aparoy","doi":"10.1016/j.jmgm.2024.108940","DOIUrl":"10.1016/j.jmgm.2024.108940","url":null,"abstract":"<div><div>Human 5-lipoxygenase (LOX) is a non-heme, Fe-containing LOX which catalyses the conversion of arachidonic acid (AA) to leukotriene A₄ (LTA₄). LTA₄ is subsequently converted to cysteinyl-LTs and LTB₄ that cause bronchoconstriction and act as chemotactic and chemokinetic agent on human leukocytes, respectively. Leukotrienes play significant roles in inflammation in asthma, cardiovascular diseases, allergic rhinitis, atopic dermatitis, inflammatory bowel disease, rheumatoid arthritis, psoriasis and many more. Thus, in order to suppress LT formation for the management of such diseases, the intrinsic details of the structure of 5-LOX are crucial for the design/development of 5-LOX inhibitors. Here, we deciphered the role of various amino acids at the allosteric site of 5-LOX through molecular dynamics simulations. 3-<em>O</em>-Acetyl-11-keto-beta-boswellic acid (AKBA), a well-recognized allosteric inhibitor of 5-LOX, was used as reference compound. The consequences of amino acid mutations (R101, E108, H130, E134) on AKBA binding have been studied <em>in silico</em>. The changes were characterized at the interaction level. Our observations provide structural insights into crucial residues which are important for stabilizing the ligand at the allosteric site. Principal component analysis (PCA) was applied to the molecular dynamics simulation data to identify the structural fluctuations in the 5-LOX structure. The derived mechanistic details of allosteric 5-LOX inhibition may facilitate the development of novel therapeutics targeting 5-LOX.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108940"},"PeriodicalIF":2.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971215","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}

{"title":"Exploring the drug delivery capabilities of Nb2C MXene functionalized with oxygen and fluorine: A DFT study","authors":"Mahmoud A.S. Sakr ,&nbsp;Hazem Abdelsalam ,&nbsp;Nahed H. Teleb ,&nbsp;Mohamed A. Saad ,&nbsp;Omar H. Abd-Elkader ,&nbsp;Yushen Liu ,&nbsp;Qinfang Zhang","doi":"10.1016/j.jmgm.2024.108937","DOIUrl":"10.1016/j.jmgm.2024.108937","url":null,"abstract":"<div><div>MXenes quantum dots (QDs), including Nb₂C, Nb₂CO₂, and Nb₂CF₂, are emerging materials with exceptional structural, electronic, and optical properties, making them highly suitable for biomedical applications. This study investigates the structural optimization, stability, electronic properties, and drug-loading potential of these QDs using fluorouracil (Flu) as a model drug. Structural analyses show that the functionalization of Nb₂C with O and F atoms enhances stability, with binding energies (BEs) of 7.335, 8.154, and 6.704 eV for Nb₂C, Nb₂CO₂, and Nb₂CF₂, respectively. The drug-loading study reveals that Nb₂C exhibits the highest adsorption energy of −6.775 eV at the surface site (2.053 Å), while Nb₂CO₂ and Nb₂CF₂ demonstrate weaker interactions with adsorption energies of −2.163 eV and −0.933 eV, respectively. Non-covalent interaction (NCI) and natural bond orbital (NBO) analyses show significant changes in electron density distribution upon drug interaction, with the natural charge on the O7 atom in Flu shifting slightly upon interaction. Optical property investigations indicate a blue shift in the absorption spectra for Nb₂CO₂ (<em>λ</em>_max = 764.76 nm) and Nb₂CF₂ (<em>λ</em>_max = 1108.71 nm), compared to Nb₂C (<em>λ</em>_max = 2612.00 nm), confirming the tunability of these materials for therapeutic applications. By addressing key challenges in drug delivery, such as stability, controlled release, and interaction strength, this study establishes Nb₂CO₂ and Nb₂CF₂ as promising nanocarriers, with the potential to improve drug efficacy and minimize side effects in targeted cancer therapies.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108937"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931938","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}