Journal of Molecular Modeling最新文献

{"title":"Mechanism of wetting by anionic surfactants with different polar groups on hydrophilic and hydrophobic nano-silica","authors":"Jiangshi Zhang,&nbsp;Yanan Wang,&nbsp;Hongfu Jia,&nbsp;Kai Wang,&nbsp;Yulu Jia,&nbsp;Xiaofeng Ren,&nbsp;Yongtun Li,&nbsp;Linquan Tong","doi":"10.1007/s00894-025-06384-x","DOIUrl":"10.1007/s00894-025-06384-x","url":null,"abstract":"<div><h3>Context</h3><p>With advancing technology, the hazards of hydrophilic and hydrophobic nano-silica dust have become increasingly apparent. Surfactants are widely used in dust control; however, their performance is primarily determined by their polar groups. To investigate the effect of various polar groups of anionic surfactants on the wettability of hydrophilic and hydrophobic nanosilica. The results indicate that the electronegativity of the electrostatic potential on the hydroxylated silica surface is relatively strong, the larger the electrostatic potential difference (ΔESP) between the surface binding sites and the polar groups of the surfactant, the less favorable the surface is for hydrophobic modification. Additionally, C and O atoms tend to form smaller negative electrostatic potentials compared to S and O atoms, with polar group activity ranked as carboxylate &gt; sulfonate &gt; benzene sulfonate &gt; sulfate. The interaction between SiO2-OH surfaces and water molecules is approximately 3.4 times stronger than that of SiO2-CH3 surfaces. The interaction between water molecules and the SiO2-OH surface is primarily governed by van der Waals forces, whereas the interaction between water molecules and the SiO2-CH3 surface is mainly driven by electrostatic forces. The polar groups of the surfactant are distributed in the aqueous phase, while the nonpolar groups interact with the surface through electrostatic interactions. The hydration layer surrounding the polar groups of hydrophilic surfaces is primarily stabilized by strong hydrogen bonding with water molecules. In contrast, for hydrophobic nano-silica surfaces, the hydration layer is influenced by both van der Waals forces and weaker hydrogen bonding interactions. The SiO2-CH3 surface cannot form hydrogen bonds, while the SiO2-OH surface has a strong capacity to stably form hydrogen bonds with carboxylate and sulfate groups. Hydrogen bonding is an essential factor in wetting. The polar group COO- is suitable for controlling hydrophilic and hydrophobic nano-silica dust. These findings provide theoretical and technical references for the selection, application, and design of surfactants in nano-silica dust control.</p><h3>Methods</h3><p>To elucidate the effects of various polar groups of anionic surfactants on the wetting of hydrophilic and hydrophobic nano-silica, quantum chemical calculations and molecular dynamics simulations were used to investigate the interfacial adsorption and wetting behavior of anionic surfactants with identical chain lengths but different polar groups on these surfaces.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 6","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125755","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":"QTAIM view of Ru–Ru bonding in a series of tri-ruthenium hydride clusters: [{CpRu(μ-H)}3(μ3-BH)], [{CpRu(μ-H)}3(μ3-H)2], [{CpRu(CO)}3(μ-BO)(μ-H)2], and [{CpRu(μ-H)}3(μ3-AlEt)]","authors":"Noorhan Ali Hamza,&nbsp;Haider Ali Hamza,&nbsp;Muhsen Abood Muhsen Al-Ibadi,&nbsp;Emad Salaam Abood,&nbsp;Ali R. Khudhair","doi":"10.1007/s00894-025-06395-8","DOIUrl":"10.1007/s00894-025-06395-8","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Context&lt;/h3&gt;&lt;p&gt;The ruthenium–ruthenium and ruthenium-ligand bonding interactions in the [{CpRu(μ-H)} &lt;sub&gt;3&lt;/sub&gt;(μ&lt;sup&gt;3&lt;/sup&gt;-BH)](&lt;b&gt;1&lt;/b&gt;), [{CpRu(μ-H)}&lt;sub&gt;3&lt;/sub&gt;(μ&lt;sup&gt;3&lt;/sup&gt;-H)&lt;sub&gt;2&lt;/sub&gt;](&lt;b&gt;2&lt;/b&gt;), [{CpRu(CO)}&lt;sub&gt;3&lt;/sub&gt;(μ-BO)(μ-H)&lt;sub&gt;2&lt;/sub&gt;](&lt;b&gt;3&lt;/b&gt;), and [{CpRu(μ-H)}&lt;sub&gt;3&lt;/sub&gt;(μ&lt;sup&gt;3&lt;/sup&gt;-AlEt)](&lt;b&gt;4&lt;/b&gt;) clusters were examined using density functional theory (DFT). Various parameters related to electron density, including the electron density &lt;i&gt;ρ&lt;/i&gt;(b), Laplacian ∇&lt;sup&gt;2&lt;/sup&gt;&lt;i&gt;ρ&lt;/i&gt;(b), local energy density H(b), local kinetic energy density G(b), potential energy density V(b), and bond delocalization index (A, B), were calculated using the quantum theory of atoms in a molecule (QTAIM). Other QTAIM indicators, such as the electron localization function (ELF) and source function (SF) were computed. According to the transition metal complexes referenced in the academic literature, the computed topological parameters are consistent. The calculated data have made it possible to compare the topological characteristics of related but distinct atom-to-atom interactions, including Ru–H interactions against Ru-BH, Ru-BO, and Ru-Al interactions, as well as H-bridged Ru–Ru interactions versus BH-, BO-, and Al-bridged interactions. The electron density distribution of the Ru–Ru interactions is influenced by different bridging ligands. Despite the presence of bridged hydride and boron in clusters &lt;b&gt;1&lt;/b&gt; and &lt;b&gt;3&lt;/b&gt;, H in cluster &lt;b&gt;2&lt;/b&gt;, and H and Al in the Ru–Ru interactions of &lt;b&gt;4&lt;/b&gt;, no localized bond, bond critical, or bond path was observed. However, the large delocalization indices &lt;i&gt;δ&lt;/i&gt;(Ru, Ru) indicate that significant indirect Ru–Ru interactions are mediated through bridging ligands. For clusters &lt;b&gt;1&lt;/b&gt;, &lt;b&gt;2&lt;/b&gt;, &lt;b&gt;3&lt;/b&gt;, and &lt;b&gt;4&lt;/b&gt;, we propose the following interactions for their core components: H&lt;sub&gt;3&lt;/sub&gt;-Ru–B (7c–14e), H&lt;sub&gt;5&lt;/sub&gt;-Ru (8c–12e), H&lt;sub&gt;2&lt;/sub&gt;-Ru&lt;sub&gt;3&lt;/sub&gt;-B (6c–8e), and H&lt;sub&gt;3&lt;/sub&gt;-Ru&lt;sub&gt;3&lt;/sub&gt;-Al (7c–14e). The AdNDP analysis confirms the presence of 4c–2e multicenter bonds in several Ru₃-based clusters, emphasizing the critical role of electron delocalization in stabilizing their core structures. The BO ligand has a higher delocalization index of 1.023, indicating that it shares a pair of electrons. Moreover, the delocalization index for cluster &lt;b&gt;3&lt;/b&gt;, &lt;i&gt;δ&lt;/i&gt;(Ru…O&lt;sub&gt;CO&lt;/sub&gt;), is very large at 0.576. This suggests that CO ligands play a significant role in M π-back-donation.&lt;/p&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Using the PBE1PBE hybrid functional and an effective core potential LanL2DZ basis set for the atoms of Ru as well as the all-electron 6-31G(d) basis set for the other atoms (Al, B, H, C and O), the optimizations were performed using the Gaussian 09 program. The geometries were verified as a local minimum by examining if imaginary vibrational frequencies were present after unrestricted optimization was carried out. Utilizing AIM2000 and Multiwfn software, we conducted QTA","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 6","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100363","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":"The α/β3 complex of human voltage-gated sodium channel hNav1.7 to study mechanistic differences in presence and absence of auxiliary subunit β3","authors":"Jordan Edilberto Ruiz-Castelan,&nbsp;Fernando Villa-Díaz,&nbsp;María Eugenia Castro,&nbsp;Francisco J. Melendez,&nbsp;Thomas Scior","doi":"10.1007/s00894-025-06378-9","DOIUrl":"10.1007/s00894-025-06378-9","url":null,"abstract":"<div><h3>Context</h3><p>In the context of structural interactomics, we generated a 3D model between α and β3 subunits for the hitherto unknown human voltage-gated sodium channel complex (hNa 1.7α/β3). We embedded our 3D model in a membrane lipid bilayer for molecular dynamics (MD) simulations of the sodium cation passage from the outer vestibule through the inner pore segment of our hNa 1.7 complex in presence and absence of auxiliary subunit β3 with remarkable changes close to electrophysiological study results. A complete passage could not be expected due to because the inactivated state of the underlying 3D template. A complete sodium ion passage would require an open state of the channel. The computed observations concerning side chain rearrangements for favorable cooperativity under evolutionary neighborhood conditions, favorable and unfavorable amino acid interactions, proline kink, loop, and helix displacements were all found in excellent keeping with the extant literature without any exception nor contradiction. Complex-stabilizing pairs of interacting amino acids with evolutionary neighborhood complementary were identified.</p><h3>Methods</h3><p>The following tools were used: sequence search and alignment by FASTA and Clustal Omega; 3D model visualization and homology modeling by Vega ZZ, SPDBV, Chimera and Modeller, respectively; missing sections (loops) by Alphafold; geometry optimization prior to MD runs by GROMACS 2021.4 under the CHARMM 36 force field; local healing of bad contacts by SPDBV based on its Ramachandran plots; protein-protein docking by HDOCK 2.4; membrane insertion assisted by OPM; Berendsen V-rescaling for NVT; Parrinello-Rahman and Nose-Hoover for MPT; MD analyses by VMD and XMGRACE</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 6","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00894-025-06378-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100440","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":"Unraveling the influence mechanisms of different substituents on the chemical activity of N-heterocyclic phosphines via theoretical calculations","authors":"Yilei Chen","doi":"10.1007/s00894-025-06390-z","DOIUrl":"10.1007/s00894-025-06390-z","url":null,"abstract":"<div><h3>Context</h3><p>N-Heterocyclic phosphines (NHP-H) represent a distinctive class of phosphorus-containing heterocycles characterized by “polarity-inverted” P–H bonds. These unique bonds facilitate a wide array of P–H reactions, rendering NHP-H compounds promising candidates for applications in organocatalysis. Although significant advancements have been made in NHP-H research, the experimental quantification of their reactivity parameters poses considerable challenges due to their high reactivity. Furthermore, the influence of various substituents on the chemical activity of NHP-H compounds remains insufficiently understood. This study examines eight NHP-H compounds with varying substituents. The findings indicate that electron-donating substituents decrease the P–H bond order, increase the negative charge on the phosphorus atom, and enhance nucleophilicity. Conversely, electron-withdrawing substituents exhibit opposite effects. Furthermore, substituents influence the local electron attachment energy of the phosphorus atom, thereby affecting reactivity in proton-transfer reactions. According to conceptual density functional theory, electron-donating substituents are associated with lower electrophilicity and higher nucleophilicity indices, whereas electron-withdrawing substituents demonstrate the opposite trend. Charge-transfer spectra suggest that electron-donating substituents reduce the excitation energy of NHP-H, thereby increasing its reactivity. Additionally, IRI analysis indicates that electron-donating substituents weaken the P–H bond, while electron-withdrawing substituents strengthen it, along with alterations in other intramolecular interactions.</p><h3>Methods</h3><p>The study utilized the M06-2X functional in conjunction with the def2-TZVP basis set within the SMD model, employing acetonitrile as the solvent, to perform structural optimization and frequency analysis of NHP-H compounds. Computational analyses were conducted using Gaussian 09 software, with 30 excited states calculated for each compound. Multiwfn software facilitated the determination of atomic dipole moment-corrected Hirshfeld population, local electron attachment energy, the Interaction Region Indicator, and charge-transfer spectrum, which were subsequently visualized using VMD 1.9.3. Additionally, GaussView 6.0.16 software was employed to generate three-dimensional molecular configurations and prepare input files.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 6","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00894-025-06390-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100361","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":"Synergistic in silico exploration of some pyrazole-based potential anticancer agents: a DFT, molecular docking, and molecular dynamics study","authors":"Pratyashee Barukial,&nbsp;Rajib Nandi,&nbsp;Nipu Kumar Das,&nbsp;Rituraj Barman,&nbsp;Benzir Ahmed,&nbsp;Gunolla Nagendraprasad,&nbsp;Tamal Banerjee,&nbsp;Bipul Bezbaruah","doi":"10.1007/s00894-025-06385-w","DOIUrl":"10.1007/s00894-025-06385-w","url":null,"abstract":"<div><h3>Context</h3><p>Understanding the interaction between therapeutic molecules with in vivo receptors is very essential in developing potential anticancer agents. In recent years, pyrazole derivatives have been evolving as a significant bioactive candidate due to their remarkable pharmacological properties in novel drug design and discovery. Herein, we present a comprehensive computational and theoretical analysis of some selected pyrazole derivatives with potential anticancer properties, employing quantum chemical calculations, molecular docking, and molecular dynamics simulation.</p><h3>Method</h3><p>In this study, quantum chemical calculations were employed using density functional theory (DFT) with B3LYP functional and 6–31G(d,p) basis set in Gaussian16 to investigate the electronic properties and intermolecular interactions of pyrazole derivatives. Natural bond orbital (NBO) analysis was performed to explore charge distribution and donor–acceptor interactions. Similarly, advanced topological analyses, viz., reduced density gradient (RDG), quantum theory of atoms in molecules (QTAIM), electron localisation function (ELF), localised orbital indicator (LOL), and electrostatic potential (ESP), to characterise intermolecular interactions and electron density features. Molecular docking studies were conducted to assess the binding affinity of the pyrazole derivatives with DNA (PDB ID: 2m2c), specifically focussing on interactions with base pairs. Molecular dynamics simulations were employed to examine the stability and characteristics of interactions over a prolonged timescale. This comprehensive approach integrates quantum chemical tools, molecular docking, and molecular dynamics simulations to elucidate the interaction mechanisms between pyrazole derivatives and DNA nucleobases, enhancing their potential novelty as anticancer agents.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 6","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100362","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":"Unveiling the influence of fastest nobel prize winner discovery: alphafold’s algorithmic intelligence in medical sciences","authors":"Niki Najar Najafi,&nbsp;Reyhaneh Karbassian,&nbsp;Helia Hajihassani,&nbsp;Maryam Azimzadeh Irani","doi":"10.1007/s00894-025-06392-x","DOIUrl":"10.1007/s00894-025-06392-x","url":null,"abstract":"<div><h3>Context</h3><p>AlphaFold’s advanced AI technology has transformed protein structure interpretation. By predicting three-dimensional protein structures from amino acid sequences, AlphaFold has solved the complex protein-folding problem, previously challenging for experimental methods due to numerous possible conformations. Since its inception, AlphaFold has introduced several versions, including AlphaFold2, AlphaFold DB, AlphaFold Multimer, Alpha Missense, and AlphaFold3, each further enhancing protein structure prediction. Remarkably, AlphaFold is recognized as the fastest Nobel Prize winner in science history. This technology has extensive applications, potentially transforming treatment and diagnosis in medical sciences by reducing drug design costs and time, while elucidating structural pathways of human body systems. Numerous studies have demonstrated how AlphaFold aids in understanding health conditions by providing critical information about protein mutations, abnormal protein–protein interactions, and changes in protein dynamics. Researchers have also developed new technologies and pipelines using different versions of AlphaFold to amplify its potential. However, addressing existing limitations is crucial to maximizing AlphaFold’s capacity to redefine medical research. This article reviews AlphaFold’s impact on five key aspects of medical sciences: protein mutation, protein–protein interaction, molecular dynamics, drug design, and immunotherapy.</p><h3>Methods</h3><p>This review examines the contributions of various AlphaFold versions AlphaFold2, AlphaFold DB, AlphaFold Multimer, Alpha Missense, and AlphaFold3 to protein structure prediction. The methods include an extensive analysis of computational techniques and software used in interpreting and predicting protein structures, emphasizing advances in AI technology and its applications in medical research.</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":"31 6","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090995","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":"Molecular dynamics simulation of TNT/PYRN cocrystal PBXs","authors":"Yu-hang Han,&nbsp;Xin-yi Li,&nbsp;Zhong-liang Ma,&nbsp;Bao-guo Wang,&nbsp;Ji-hang Du,&nbsp;Yu Yang,&nbsp;Hong-wei Zhao,&nbsp;Qing-jun Jin,&nbsp;Peng-yu Bi","doi":"10.1007/s00894-025-06394-9","DOIUrl":"10.1007/s00894-025-06394-9","url":null,"abstract":"<div><h3>Context</h3><p>The ternary eutectic system comprising trinitrotoluene (TNT) and pyranidine (PYRN) exhibits potential as a moderate-energy explosive compound characterized by reduced sensitivity. Recently, this composition can be a suitable alternative to TNT in the development of low-vulnerability explosive formulations, thus providing a promising alternative for future applications in the field of energetic materials. However, the changes in the structure and properties of eutectic explosives and their intrinsic causes for these changes have been rarely explored. Here, we construct a theoretical model of the TNT/PYRN eutectic system and integrates a diverse array of polymer additives, including butadiene rubber (BR), ethylene–vinyl acetate copolymer (EVA), polyethylene glycol (PEG), fluorinated polymer (F2603), and polyvinylidene fluoride (PVDF), into five distinct cleavage planes ((1 0 0), (0 1 0), (0 1 − 1), (1 0 0), and (1 0 − 1)) within the eutectic matrix. We found that the synthesis of polymer-bonded explosives (PBXs) is achieved through the integration of the aforementioned polymers into the TNT/PYRN eutectic system. This investigation elucidated the influence of various polymer matrices on the structural integrity, critical bond distances for initiation, mechanical attributes, and detonative behavior of the resultant PBXs. Within the corpus of five PBX models examined, the TNT/PYRN/F2603 configuration showed the supremum in binding energetics and the infimum in critical bond lengths, which portends superior stability, interfacial harmony, and a minimized propensity for unintended initiation. Furthermore, the TNT/PYRN/F2603 system was delineated by its enhanced capability for explosive initiation. Note importantly that the TNT/PYRN/F2603 model exhibited pre-eminence in its aggregate performance metrics, corroborating the hypothesis that F2603 constitutes a preferential binder candidate for PBX formulations predicated on the TNT/PYRN eutectic composite.</p><h3>Methods</h3><p>Utilizing the Materials Studio computational platform, the physicochemical attributes of the TNT/PYRN eutectic-based polymer-bonded explosives (PBXs) were anticipated via molecular dynamics (MD) simulations. The MD protocol was executed with a temporal increment of 1 fs, encompassing an aggregate simulation span of 2 ns. An isothermal-isobaric (NPT) thermodynamic ensemble was employed for the duration of the 2 ns MD trajectory. The COMPASS empirical force field was utilized to model interatomic interactions, and the thermal parameter was maintained at a constant 295 K throughout the simulation campaign.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 6","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090996","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":"Structural dynamics of LDL receptor interactions with E498A and R499G variants of PCSK9","authors":"Nur Alya Amirah Azhar,&nbsp;Yung-An Chua,&nbsp;Hapizah Nawawi,&nbsp;Siti Azma Jusoh","doi":"10.1007/s00894-025-06380-1","DOIUrl":"10.1007/s00894-025-06380-1","url":null,"abstract":"<div><h3>Context</h3><p>The low-density lipoprotein receptor (LDLR) regulates cholesterol uptake by mediating the hepatic clearance of plasma low-density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin/kexin type-9 (PCSK9) attenuates LDLR function by binding to the LDLR, leading to its lysosomal degradation and preventing the total depletion of circulating LDL-C. However, pathogenic PCSK9 variants can reduce LDLR availability, significantly increase plasma LDL-C levels. Despite this understanding, the detailed molecular mechanism of LDLR-PCSK9 interaction remains unclear due to the incomplete LDLR structure. This study uses molecular dynamics (MD) simulations to predict LDLR structural dynamics upon binding to PCSK9. Furthermore, PCSK9 variants, E498A and R499G, that were identified in Malaysian FH patients were investigated for their mutational effects. Throughout the simulations, PCSK9 remained stable, while LDLR explored a larger conformational space. The LDLR-PCSK9 wild-type (WT) complex showed minimal changes, while the LDLR-PCSK9(R499G) complex exhibited pronounced conformational rearrangement. The MM/GBSA analysis revealed that the LDLR-PCSK9(E498A) complex had the highest binding affinity (− 63.81 kcal/mol), followed by the WT complex (− 33.07 kcal/mol), and LDLR-PCSK9(R499G) (− 24.21 kcal/mol). These findings offer novel insights into the dynamic interactions between LDLR and PCSK9, highlighting the role of structural flexibility in their relationship. Further MD simulation studies with the complete LDLR structure as well as experimental validation are needed to elucidate the molecular mechanisms underlying LDLR-PCSK9-mediated cholesterol homeostasis.</p><h3>Methods</h3><p>The initial structure of the wild-type (WT) LDLR-PCSK9 complex was obtained from PDB ID 3P5C, and the PCSK9 mutant structures (E498A and R499G) were modeled using the SPDBV program. MD simulations for each complex—LDLR-PCSK9 WT, LDLR-PCSK9(E498A), and LDLR-PCSK9(R499G)—were conducted using the GROMACS package with the CHARMM36m force field. The simulations were performed at 310.15 K with 2-fs timesteps under the isothermal-isobaric (NPT) ensemble, with each run lasting 500 ns. Including triplicates, the total duration of MD simulation time for all complexes amounted to 3.5 μs.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 6","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084897","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 new selenium nanomaterial: structural insights, nonlinear optical properties (DFT study), and biological potential","authors":"Rumyana Yankova,&nbsp;Tsvetelina Yotova,&nbsp;Mario Avramov,&nbsp;Daiana Benkova,&nbsp;Dimitar Dimov,&nbsp;Aneliya Kostadinova,&nbsp;Pavel Markov","doi":"10.1007/s00894-025-06387-8","DOIUrl":"10.1007/s00894-025-06387-8","url":null,"abstract":"<div><h3>Context</h3><p>This study investigates the synthesis, structural characteristics, thermal properties, and biological activity of the double selenate salt Na₂Cd(SeO₄)₂·2H₂O. The synthesis of this compound was driven by the need for novel materials with potential applications in medicinal chemistry and materials science. The structural integrity and physicochemical properties of Na₂Cd(SeO₄)₂·2H₂O were confirmed through a series of characterization techniques, including FT-IR spectroscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), dynamic light scattering (DLS), and zeta potential measurements. The thermal behavior of the compound, exhibiting a multi-stage decomposition pattern, provides important insights into its stability and transformation mechanisms, essential for its potential use in various applications. Biological testing, conducted on the HepG2 liver cancer cell line, revealed a dose-dependent cytotoxic effect, with morphological changes and cytoskeletal disruption at higher concentrations, highlighting the compound’s anticancer potential. The compound also demonstrated a high zeta potential, indicating good colloidal stability and suggesting favorable bioavailability. These findings underscore the relevance of Na₂Cd(SeO₄)₂·2H₂O for biomedical applications, particularly in anticancer therapies, where its unique combination of properties may offer therapeutic advantages.</p><h3>Methods</h3><p>Quantum chemical calculations were performed using density functional theory (DFT) to gain insights into the electronic structure, molecular geometry, and nonlinear optical (NLO) properties of Na₂Cd(SeO₄)₂·2H₂O. Molecular electrostatic potential (MEP) mapping revealed nucleophilic and electrophilic activity regions, pointing to possible reactive sites. Frontier molecular orbital (FMO) analysis indicated a moderate HOMO–LUMO energy gap, suggesting a balance between stability and reactivity. Thermal decomposition stages were characterized using TGA and DSC, with identifiable mass loss steps corresponding to water release and selenium dioxide formation. In vitro biological evaluation was conducted on HepG2 cells using MTT assays, immunofluorescence staining, and morphological analysis. The IC₅₀ value was established at approximately 0.05 µg/ml. Zeta potential and DLS analyses were employed to assess colloidal behavior and particle distribution. Together, these methodologies support the promising physicochemical and biological profile of Na₂Cd(SeO₄)₂·2H₂O, justifying its further investigation for nanomedicine and drug delivery applications.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 6","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084896","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 constant pH molecular dynamics and experimental study on the effect of different pH on the structure of urease from Sporosarcina pasteurii","authors":"Yifei Zheng,&nbsp;Lingling Wu,&nbsp;Qiucai Zhang,&nbsp;Lin Hu,&nbsp;Yakun Tian,&nbsp;Min Wang,&nbsp;Huaimiao Zheng,&nbsp;Zhijun Zhang","doi":"10.1007/s00894-025-06369-w","DOIUrl":"10.1007/s00894-025-06369-w","url":null,"abstract":"<div><h3>Context</h3><p>Urease is pivotal in microbial-induced calcium carbonate precipitation (MICP), where its catalytic efficiency directly governs calcium carbonate formation. However, practical MICP applications in extreme environments (e.g., acidic mine drainage, industrial waste sites) are hindered by limited understanding of urease behavior under extreme pH conditions. This study combines laboratory experiments and constant pH molecular dynamics (CpHMD) simulations to investigate how pH variations (3–11) affect the structural stability of <i>Sporosarcina pasteurii</i> urease, focusing on its α-subunit (PDB: 4CEU). Experimental validation identified pH 7–8 as optimal for urease activity, aligning with molecular dynamics results showing minimal structural deviations (RMSD) and stable protonation states under neutral to mildly alkaline conditions. Extreme pH (3, 4, 11) disrupted active-site geometry and induced charge fluctuations, impairing catalytic function. CpHMD simulations revealed that the α-subunit retains structural integrity at pH 7–8, suggesting potential reassembly post-environmental stress. This work bridges gaps in enzymatic stability under harsh conditions, offering insights for optimizing MICP in geotechnical and environmental remediation applications.</p><h3>Methods</h3><p>The study combined experimental and computational approaches. <i>Sporosarcina pasteurii</i> urease activity was experimentally assessed across pH 3–11 by monitoring urea hydrolysis-induced conductivity changes. Computational analyses employed GROMACS constant pH with the CHARMM36 force field to perform pH-dependent molecular dynamics simulations. The urease structure was solvated, neutralized, energy-minimized, and subjected to constant pH simulations. Structural stability, active site dynamics, and protonation states of titratable residues were analyzed via RMSD, hydrogen bonds, solvent-accessible surface area (SASA), and Epock 1.0.5. Free energy landscapes and residue interactions were evaluated using principal component analysis (PCA) and λ-dynamics. Experimental data were processed with OriginPro 2024b and Python, linking pH-induced conformational shifts to enzymatic function.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 6","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090997","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}