The Journal of Physical Chemistry B最新文献

{"title":"MD Simulations of Peptide-Containing Electrospray Droplets: Effects of Parameter Settings on the Predicted Mechanisms of Gas Phase Ion Formation.","authors":"Kasra Hanifi, Pablo M Scrosati, Lars Konermann","doi":"10.1021/acs.jpcb.4c01241","DOIUrl":"10.1021/acs.jpcb.4c01241","url":null,"abstract":"<p><p>Electrospray ionization (ESI) mass spectrometry is widely used for interrogating peptides, proteins, and other biomolecular analytes. A growing number of laboratories use molecular dynamics (MD) simulations for uncovering ESI mechanisms by modeling the behavior of highly charged nanodroplets. The outcome of any MD simulation depends on certain assumptions and parameter settings, and it is desirable to optimize these factors by benchmarking computational data against experiments. Unfortunately, benchmarking of ESI simulations is difficult because experimentally generated gaseous ions do not generally retain any features that would reveal their formation pathway [e.g., the charged residue mechanism (CRM) or the ion evaporation mechanism (IEM)]. Here, we tackle this problem by examining the effects of various MD settings on the ESI behavior of the 9-residue peptide bradykinin in acidic aqueous droplets. Several parameters were found to significantly affect the kinetic competition between peptide IEM and CRM. By systematically probing the droplet behavior, we uncovered problems associated with certain settings, including peptide/solvent temperature imbalances, unexpected peptide deceleration during IEM, and a dependence of the ESI mechanism on the water model. We also noted different simulation outcomes for different force fields. On the basis of comprehensive tests, we propose a set of \"best practice\" parameter settings for MD simulations of ESI droplets. The strategies used here should be transferable to other types of droplet simulations, paving the way toward a more solid understanding of ESI mechanisms.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141304905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure and Dynamics of Aqueous 2-Aminothiazole/NaCl Electrolytes at Electrified Interfaces.","authors":"Steffen Jeschke, Philipp Eiden, Qiushi Deng, Ivan S Cole, Patrick Keil","doi":"10.1021/acs.jpcb.4c01479","DOIUrl":"10.1021/acs.jpcb.4c01479","url":null,"abstract":"<p><p>A computational study was performed to investigate the dynamics of aqueous electrolytes containing organic corrosion inhibitors near electrified interfaces by using the constant-charge model in classical molecular dynamics simulations. The results showed that when inhibitors form films at the interface, the surface charge of the electrode causes displacement of the molecules, referred to as electroporation. The hydrophobicity of the inhibitor molecules affects both the stability of the films and their recovery time. This study highlights the value of computational investigations of the dynamics within inhibitor films as a complementary approach to the traditional focus on inhibitor-substrate interactions, leading to deeper insights into the mechanisms of corrosion inhibition mechanisms.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Key Binding Interactions Between the Cardiac L-Type Calcium Channel and Calmodulin Using Molecular Dynamics Simulations.","authors":"D'Artagnan Greene, Yohannes Shiferaw","doi":"10.1021/acs.jpcb.4c02251","DOIUrl":"10.1021/acs.jpcb.4c02251","url":null,"abstract":"<p><p>Defects in the binding of the calcium sensing protein calmodulin (CaM) to the L-type calcium channel (Ca_V1.2) or to the ryanodine receptor type 2 (RyR2) can lead to dangerous cardiac arrhythmias with distinct phenotypes, such as long-QT syndrome (LQTS) and catecholaminergic ventricular tachycardia (CPVT). Certain CaM mutations lead to LQTS while other mutations lead to CPVT, but the mechanisms by which a specific mutation can lead to each disease phenotype are not well-understood. In this study, we use long, 2 μs molecular dynamics simulations and a multitrajectory approach to identify the key binding interactions between the IQ domain of Ca_V1.2 and CaM. Five key interactions are found between Ca_V1.2 and CaM in the C-lobe, 1 in the central linker, and 2 in the N-lobe. In addition, while 5 key interactions appear between residues 120-149 in the C-lobe of CaM when it interacts with Ca_V1.2, only 1 key interaction is found within this region of CaM when it interacts with the RyR2. We show that this difference in the distribution of key interactions correlates with the known distribution of CaM mutations that lead to LQTS or CPVT. This correlation suggests that a disruption of key binding interactions is a plausible mechanism that can lead to these two different disease phenotypes.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, Fluorescence, and Bioactivity of Novel Isatin Derivatives.","authors":"Yi-Xin Dong, Li-Xin Gao, Qing Cao, Zi-Tong Cao, Su-Ya Gan, Jia Li, Yun-Long Zhu, Yu-Bo Zhou, Chun Zhang, Wen-Long Wang","doi":"10.1021/acs.jpcb.4c02561","DOIUrl":"10.1021/acs.jpcb.4c02561","url":null,"abstract":"<p><p>The isatin group is widespread in nature and is considered to be a privileged building block for drug discovery. In order to develop novel SHP1 inhibitors with fluorescent properties as tools for SHP1 biology research, this work designed and synthesized a series of isatin derivatives. The presentive compound <b>5a</b> showed good inhibitory activity against SHP1^PTP with IC₅₀ of 11 ± 3 μM, displayed about 92% inhibitory rate against MV-4-11 cell proliferation at the concentration of 20 μM, exhibited suitable fluorescent properties with a long emission wavelength and a large Stokes shift, and presented blue fluorescent imaging in HeLa cells with low cytotoxicity. This study could offer chemical tool to further understand SHP1 biology and develop novel SHP1 inhibitors in therapy.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controlling Ionic Conductivity in Organometallic Ionic Liquids through Light-Induced Coordination Polymer Formation and Thermal Reversion.","authors":"Tomoyuki Mochida, Masato Shimada, Ryota Inoue, Ryo Sumitani, Yusuke Funasako, Hiroki Yamada","doi":"10.1021/acs.jpcb.4c02150","DOIUrl":"10.1021/acs.jpcb.4c02150","url":null,"abstract":"<p><p>Owing to their high ionic conductivity and negligible vapor pressure, ionic liquids (ILs) find applications in various electronic devices. However, fabricating IL-based photocontrollable devices remains a challenge. In this study, we developed organometallic ILs with reversible light- and heat-controlled ionic conductivities for potential use in tunable devices. The physical properties and stimulus responses of ILs containing a cationic sandwich Ru complex with two coordinating substituents were investigated. UV photoirradiation of these ILs triggered cation photodissociation, resulting in their transformation into viscoelastic coordination polymers wherein the coordinating substituents bridged the Ru centers. Owing to the anion coordination, salts with coordinating anions such as CF₃SO₂NCN^-, B(CN)₄^-, and BF₂(CN)₂^- exhibited faster response and higher conversion than those with noncoordinating anions including (FSO₂)₂N^- and (CF₃SO₂)₂N^-. All photoproducts reverted to their original ILs upon heating, except for the photoproduct of the BF₂(CN)₂ salt, which decomposed upon heating. Light- and heat-induced reversible changes occur in most cases between the high-ionic-conductive IL state and low-ionic-conductive coordination polymer state. Unlike previously reported ILs with three or one cation substituent, the current ILs exhibited both high reactivity and large ionic conductivity changes.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141299391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curvature Footprints of Transmembrane Proteins in Simulations with the Martini Force Field.","authors":"Elio A Cino, D Peter Tieleman","doi":"10.1021/acs.jpcb.4c01385","DOIUrl":"10.1021/acs.jpcb.4c01385","url":null,"abstract":"<p><p>Membranes play essential roles in biological systems and are tremendously diverse in the topologies and chemical and elastic properties that define their functions. In many cases, a given membrane may display considerable heterogeneity, with localized clusters of lipids and proteins exhibiting distinct characteristics compared to adjoining regions. These lipid-protein assemblies can span nanometers to micrometers and are associated with cellular processes such as transport and signaling. While lipid-protein assemblages are dynamic, they can be stabilized by coupling between local membrane composition and shape. Due to the inherent difficulty in resolving atomistic details of membrane proteins in their native lipid environments, these complexes are notoriously challenging to study experimentally; however, molecular dynamics (MD) simulations might be a viable alternative. Here, we aim to assess the utility of coarse-grained (CG) MD simulations with the Martini force field for studying membrane curvature induced by transmembrane (TM) proteins that are reported to generate local curvature. The direction and magnitude of curvature induced by five different TM proteins, as well as certain lipid-protein and protein-protein interactions, were found to be in good agreement with available reference data.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141299392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantum Mechanics-Based Fast and Reliable Prediction of Binding Pose Structures.","authors":"Amar Y Al-Ansi, Gamal H Al-Shawesh, Xiao Ru, Zijing Lin","doi":"10.1021/acs.jpcb.4c02596","DOIUrl":"10.1021/acs.jpcb.4c02596","url":null,"abstract":"<p><p>Predicting the binding poses of docking with an accurate estimation of binding energies is highly important but very challenging in computational drug design. A quantum mechanics (QM) calculation-based docking approach considering multiple conformations and orientations of the ligand is introduced here to tackle the problem. This QM docking consists of three steps: generating an ensemble of binding poses with a conventional docking simulation, computing the binding energies with self-consistent charge density functional theory tightly binding with dispersion correction (DFTB-D) to selecting the 10 top binding modes, and optimizing the selected binding mode structures using the ONIOM(DFTB:PM7) technique to determine the binding poses. The ONIOM(DFTB-D:PM6) docking approach is tested on 121 ligand-receptor biocomplexes with the crystal structures obtained from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB). The result shows that the new method is highly satisfactory for the accurate prediction of the binding poses. The new docking method should be beneficial to structure-based drug design.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atomistic Simulation of Hf-Pyridyl Amido-Catalyzed Chain Transfer Alkene Polymerization Reaction and Its Machine Learning for Extraction of Essential Descriptors: Effect of Microscopic Steric Hindrance on the Monomer Insertion Process.","authors":"Shuhei Kanesato, Katsuhisa Yasoshima, Kentaro Matsumoto, Nana Misawa, Yuichi Suzuki, Nobuaki Koga, Masataka Nagaoka","doi":"10.1021/acs.jpcb.4c01303","DOIUrl":"10.1021/acs.jpcb.4c01303","url":null,"abstract":"<p><p>The microscopic effects of each substituent of the Hf catalyst and the growing polymer on the monomer insertion process were investigated for Hf-pyridyl amido-catalyzed coordinative chain transfer polymerization using the Red Moon method. Since the Hf catalyst has two reaction sites, <i>cis</i>- and <i>trans</i>-sites, we separately applied the appropriate analysis methods to each one, revealing that the naphthalene ring influenced monomer insertion at the <i>cis</i>-one, while the <i>i</i>-Pr group and the hexyl group of the adjacent 1-octene unit did the <i>trans</i>-one. It was interesting to find that the hexyl group of the 1-octene-inserted catalyst (oHfCat) pushes the naphthalene ring toward the <i>cis</i>-site and narrows the space at the <i>cis</i>-site, thus indirectly creating a steric hindrance to <i>cis</i>-insertions. Further, the relative position of the Hf catalyst and the growing polymer was found to be strongly influenced by the patterns of insertion reactions, i.e., <i>cis</i>- or <i>trans</i>-insertions. In particular, it was clarified that, after <i>trans</i>-insertions, the growing polymer on the Hf atom covers the <i>cis</i>-site, making <i>cis</i>-insertion less likely to occur. These studies reveal the microscopic effects of the catalyst substituents and the growing polymer on the catalyst during the polymerization reaction process; these microscopic analyses using the RM method should provide atomistic insights that are not easy to obtain experimentally for advanced catalyst design and polymerization control.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Unimers to Polymersomes Transition in Pluronic Blends for Controlled and Designated Drug Conveyance.","authors":"Divya Patel, Nitumani Tripathi, Payal Vaswani, Germán Pérez-Sánchez, Dhiraj Bhatia, Ketan Kuperkar, João A P Coutinho, Pratap Bahadur","doi":"10.1021/acs.jpcb.4c00561","DOIUrl":"10.1021/acs.jpcb.4c00561","url":null,"abstract":"<p><p>This study investigates the nanoscale self-assembly from mixtures of two symmetrical poly(ethylene oxide)-poly(propylene oxide)-pol(ethylene oxide) (PEO-PPO-PEO) block copolymers (BCPs) with different lengths of PEO blocks and similar PPO blocks. The blended BCPs (commercially known as Pluronic F88 and L81, with 80 and 10% PEO, respectively) exhibited rich phase behavior in an aqueous solution. The relative viscosity (η_rel) indicated significant variations in the flow behavior, ranging from fluidic to viscous, thereby suggesting a possible micellar growth or morphological transition. The tensiometric experiments provided insight into the intermolecular hydrophobic interactions at the liquid-air interface favoring the surface activity of mixed-system micellization. Dynamic light scattering (DLS) and small-angle neutron scattering (SANS) revealed the varied structural morphologies of these core-shell mixed micelles and polymersomes formed under different conditions. At a concentration of ≤5% w/v, Pluronic F88 exists as molecularly dissolved unimers or Gaussian chains. However, the addition of the very hydrophobic Pluronic L81, even at a much lower (<0.2%) concentration, induced micellization and promoted micellar growth/transition. These results were further substantiated through molecular dynamics (MD) simulations, employing a readily transferable coarse-grained (CG) molecular model grounded in the MARTINI force field with density and solvent-accessible surface area (SASA) profiles. These findings proved that F88 underwent micellar growth/transition in the presence of L81. Furthermore, the potential use of these Pluronic mixed micelles as nanocarriers for the anticancer drug quercetin (QCT) was explored. The spectral analysis provided insight into the enhanced solubility of QCT through the assessment of the standard free energy of solubilization (Δ<i>G</i>°), drug-loading efficiency (DL%), encapsulation efficiency (EE%), and partition coefficient (<i>P</i>). A detailed optimization of the drug release kinetics was presented by employing various kinetic models. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] MTT assay, a frequently used technique for assessing cytotoxicity in anticancer research, was used to gauge the effectiveness of these QCT-loaded mixed nanoaggregates.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Iron Oxide Phases on the Magnetic Induction Heating Capacity of Mesoporous 45SiO₂-16.5CaO-24.5Na₂O-6P₂O₅-8Fe₃O₄ Glass-Ceramics.","authors":"Nitu, Molongnenla Jamir, Jyoti Prasad Borah, Ananthakrishnan Srinivasan","doi":"10.1021/acs.jpcb.4c02485","DOIUrl":"10.1021/acs.jpcb.4c02485","url":null,"abstract":"<p><p>Sol-gel-based mesoporous 45SiO₂-16.5CaO-24.5Na₂O-6P₂O₅-8Fe₃O₄ bioglass-ceramics were obtained by substituting magnetite nanoparticles for CaO in a 45SiO₂-24.5CaO-24.5Na₂O-6P₂O₅ bioglass composition. To enhance the dissolution of the precursors and to vary the crystalline phases, the as-synthesized ceramic powders were processed for 1 h each at temperatures (<i>T</i>_A) between 550 and 700 °C. A gradual decline in the saturation magnetization with an increase in <i>T</i>_A was observed, which is linked to the gradual conversion of magnetite into hematite at different <i>T</i>_A > 550 °C. All of the processed samples indicated a hydroxyapatite surface layer formation in <i>in vitro</i> tests. Aqueous solutions of the ceramic processed at 600 °C exhibited superior magnetic induction capacity. Thus, the substitution of magnetite nanoparticles for CaO in the base composition, coupled with appropriate heat treatment, results in a promising bioactive glass-ceramic for magnetic hyperthermia treatment of deep-rooted cancer cells.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}