The Journal of Physical Chemistry B最新文献

{"title":"Predicting Carbonic Anhydrase Binding Affinity: Insights from QM Cluster Models.","authors":"Mackenzie Taylor, Haedam Mun, Junming Ho","doi":"10.1021/acs.jpcb.4c06393","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c06393","url":null,"abstract":"<p><p>A systematic series of QM cluster models has been developed to predict the trend in the carbonic anhydrase binding affinity of a structurally diverse dataset of ligands. Reference DLPNO-CCSD(T)/CBS binding energies were generated for a cluster model and used to evaluate the performance of contemporary density functional theory methods, including Grimme's \"3c\" DFT composite methods (r²SCAN-3c and ωB97X-3c). It is demonstrated that when validated QM methods are used, the predictive power of the cluster models improves systematically with the size of the cluster models. This provided valuable insights into the key interactions that need to be modeled quantum mechanically and could inform how the QM region should be defined in hybrid quantum mechanics/molecular mechanics (QM/MM) models. The use of r²SCAN-3c on the largest cluster model composed of 16 residues appears to be an economical approach to predicting binding trends compared with using more robust DFT methods such as ωB97M-V and provides a significant improvement compared with docking.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051079","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":"Complementary Peptide Interactions Support the Ultra-Rigidity of Polymers of De Novo Designed Click-Functionalized Bundlemers.","authors":"Dai-Bei Yang, Tianren Zhang, Jacquelyn E Blum, Christopher J Kloxin, Darrin J Pochan, Jeffery G Saven","doi":"10.1021/acs.jpcb.4c06403","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c06403","url":null,"abstract":"<p><p>Computationally designed 29-residue peptides yield tetra-α-helical bundles with <i>D</i>₂ symmetry. The \"bundlemers\" can be bifunctionally linked via thiol-maleimide cross-links at their N-termini, yielding supramolecular polymers with unusually large, micrometer-scale persistence lengths. To provide a molecularly resolved understanding of these systems, all-atom molecular modeling and simulations of linked bundlemers in explicit solvent are presented. A search over relative orientations of the bundlemers identifies a structure, wherein at the bundlemer-bundlemer interface, interior hydrophobic residues are in contact, and α-helices are aligned with a pseudocontiguous α-helix that spans the interface. Calculation of a potential of mean force confirms that the structure in which the bundlemers are in contact and colinearly aligned is a stable minimum. Analyses of hydrogen bonds and hydrophobic complementarity highlight the complementary interactions at the interface. The molecular insight provided reveals the molecular origins of bundlemer alignment within the supramolecular polymers.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051076","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":"Molecular Dynamics Insights into Water Transport Mechanisms in Polyamide Membranes: Influence of Cross-Linking Degree.","authors":"Chi Zhang, Guangle Bu, Lida Meng, Dan Lu, Sirui Tong, Zhikan Yao, Danjun Zheng, Lin Zhang","doi":"10.1021/acs.jpcb.4c06566","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c06566","url":null,"abstract":"<p><p>Polyamide (PA) membranes are widely utilized in desalination and water treatment applications, yet the mechanisms underlying water transport within these amorphous polymer materials remain insufficiently understood. To gain more insight into these problems on a microscopic scale, we employ molecular dynamics (MD) simulations to analyze the relationship between the structural properties and the water permeation behavior of PA membranes. Two distinct atomistic models of PA membranes are developed by controlling their degrees of cross-linking (DC). We then conducted a comparative analysis on their microscopic structural properties and configurations of water inside the membranes and investigated how these differences lead to different water diffusion coefficients. Our results reveal that the membrane with a lower DC exhibits higher polymer mobility and a more orderly microscopic structure, allowing the formation of pores that can hold larger water clusters as well as more transient passages between pores, both contributing to an increased water diffusion coefficient. From these observations, we can conclude that water permeability within PA membranes is governed by both the morphology of semirigid pores and the oscillatory movements of the polymer chains. Overall, these findings contribute to a deeper understanding of the intricate mechanisms governing water permeation in PA membranes and may inform the design of more efficient membranes for reverse osmosis and other water treatment technologies.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051078","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":"Ion-Ion Structural Correlation and Dynamics of Water in Aqueous NaCl Solutions with a Wide Range of Concentrations.","authors":"Khushika, Pritam Kumar Jana","doi":"10.1021/acs.jpcb.4c05252","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c05252","url":null,"abstract":"<p><p>The behavior of water in concentrated ionic solutions, including supersaturated conditions, is crucial for numerous material and energy conversion processes and fundamental research. All electrolytes whether they \"structure-make\" or \"structure-break\" the water structure lead to slower water motion. This study investigates the structure and dynamics of aqueous NaCl solutions across a wide range of concentrations. On the structural side, the primary focus is on ion-ion correlations. In terms of dynamics, we demonstrate that the slowing down of water dynamics continues even beyond the saturated state. We identify three distinct types of dynamics at large concentrations: ballistic, trapped, and diffusive. The van Hove correlation function exhibits no signs of relaxation within a time interval where particle motion is effectively halted. The system displays dynamical heterogeneities, confirmed by evaluating non-Gaussian parameters for the self-part of the van Hove function and identifying the mobile particles. These particles form clusters, with the largest sizes occurring when the non-Gaussian parameters are at their maximum. Additionally, we discuss the relaxation times associated with these systems using the incoherent intermediate scattering function and establish a connection with the mode-coupling theory.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051077","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":"Tale of Three Dithienylethenes: Following the Photocycloreversion with Ultrafast Spectroscopy and Quantum Dynamics Simulations.","authors":"Arkadiusz Jarota, Ewa Pastorczak","doi":"10.1021/acs.jpcb.4c04135","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c04135","url":null,"abstract":"<p><p>Photocycloreversion reactions of three diarylethene derivatives whose structures differ only in the placement of two sulfur atoms in the cyclopentene rings are investigated. Despite the minuscule differences between the molecules, both the yields and times of the photoreactions vary considerably. Using UV-vis and infrared femtosecond spectroscopy and quantum chemical dynamics simulations, we elucidate the relationships among the quantum yield, electronic and vibrational relaxation time, and structural properties of the dithienylethene photoswitches. We show that the local aromaticity of the molecule's central ring could be one of the predictors of the quantum yield and the rate of cycloreversion. While from the perspective of electronic dynamics, the cycloreversion is completed within a few picoseconds at most, all three derivatives exhibit much longer (10-25 ps) nuclear rearrangement times that determine the actual times of stable photoproduct formation.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044913","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":"Greater Influence of Density on the Electrical Properties of an Organic Semiconductor Glass Compared to Molecular Orientation.","authors":"Gwiwon Jang, Taewoo Kim, Junho Lee, Joonsuk Huh, Seong Eun Kim, So Youn Kim, Yasushi Koishikawa, Ohyun Kwon, Keewook Paeng","doi":"10.1021/acs.jpcb.4c06512","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c06512","url":null,"abstract":"<p><p>Physical vapor deposition is widely used in the fabrication of organic light-emitting diodes and has the potential to adjust the density and orientation through substrate temperature control, which may lead to enhanced electrical performance. However, it is unclear whether this enhanced property is because of the horizontal molecular orientation or the increased density. The effects of the density and orientation on the electrical properties of a potential electron transport material, (3-dibenzo[c,h]acridin-7-yl)phenyl)diphenylphosphine oxide (TPPO-dibenzacridine), were investigated. According to the gyration tensor analysis, TPPO-dibenzacridine resembled an oblate ellipsoid. Furthermore, these films exhibited the highest density when prepared at a substrate temperature of 87.5% of the glass transition temperature with an increase in density of approximately 1.5%. Variable angle spectroscopic ellipsometry measurements confirmed that the transition dipole moment direction of the dibenzacridine moiety, which is involved in the electrical properties, remained isotropic at this temperature. Although horizontal orientations are known to optimize their π-π overlap and improve the electrical properties, the lowest driving voltage was observed under these conditions, which led to the conclusion that the enhanced electrical properties of TPPO-dibenzacridine are greatly influenced by the increased density rather than by the molecular orientation.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035366","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":"Binding of Homeodomain Proteins to DNA with Hoogsteen Base Pair.","authors":"Kanika Kole, Jaydeb Chakrabarti","doi":"10.1021/acs.jpcb.4c08054","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c08054","url":null,"abstract":"<p><p>In DNA double helices, Hoogsteen (HG) base pairing is an alternative mode of Watson-Crick (WC) base pairing. HG bp has a different hydrogen bonding pattern than WC bp. We investigate here the binding energy of homeodomain proteins with a HG-DNA duplex, where DNA adopts a HG bp in its sequence. We observe that the presence of the HG bp increases the binding energy of both the specific and nonspecific homeodomain proteins compared to WC-DNA bps. The neutral mutation in the N-terminal basic arm of the nonspecific protein significantly changes the binding energy between nonspecific protein and HG-DNA only, while the acidic mutation significantly changes the binding energy of both the specific and nonspecific proteins with HG-DNA. The significant variation in the binding energy of the homeodomains within distinct DNA-protein complexes can be ascribed to the differences in the number of intermolecular contacts between DNA bases and protein residues. Our conformational thermodynamics calculations based on the fluctuation of microscopic conformational variables at the interface show that with increasing conformational stability and order at the interface, the binding of the homeodomain protein gets stronger.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035364","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":"Preferential Binding of a Long-Arm Porphyrin Ligand to Higher Order G-Quadruplex under Crowding Conditions.","authors":"Di Song, Tingxiao Qin, Shuyi Yan, Dongyu Li, Jialong Jie, Hongmei Su","doi":"10.1021/acs.jpcb.4c06876","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c06876","url":null,"abstract":"<p><p>Under conditions that are close to the real cellular environment, the human telomeric single-stranded overhang (∼200 nt) consisting of tens of TTAGGG repeats tends to form higher order structures of multiple G-quadruplex (G4) blocks. On account of the higher biological relevance of higher order G4 structures, ligand compounds binding to higher order G4 are significant for the drug design toward inhibiting telomerase activity. Here, we study the interaction between a cationic porphyrin derivative, 5,10,15,20-tetra{4-[2-(1-methyl-1-piperidinyl)propoxy]phenyl}porphyrin (T4), and a human telomeric G4-dimer (AG₃(T₂AG₃)₇) in the mimic intracellular molecularly crowded environment (PEG as a crowding agent) and K⁺ or Na⁺ solution (i.e., K⁺-PEG and Na⁺-PEG), by means of multiple steady-state and time-resolved spectroscopic techniques. It is revealed that the long-armed T4 selectively binds to the K⁺-PEG G4-dimer by intercalating into the cleft pocket between the two G4 blocks, since the two G4 monomers with parallel-stranded topology are stacked by head-to-tail arrangement and can offer π-stacking interface binding with T4. In contrast, the Na⁺-PEG G4-dimer with antiparallel-stranded topology adopts side-by-side arrangement of G-quartets, resulting in a lack of π-π binding sites to stabilize T4 within the cleft, and no obvious binding characteristics are observed. Interestingly, it is observed that protonation of T4 is facilitated upon binding with the K⁺-PEG G4-dimer, which can occur under physiological pH, due to the π-π stacking with two G-quartet planes that enhances the electron-rich character of the central porphyrin core of T4. Afterward, the protonated T4 displays dramatically different spectral characteristics (Soret band, Q-band, fluorescence band, and lifetime), which in turn serves as a spectral reporter for characterizing the DNA-binding event. These findings provide a mechanistic basis for developing targeted ligands that can specifically interact with higher order physiological G4 structures.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031553","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":"Structural and Dynamical Response of Lipid Bilayers to Solvation of an Amphiphilic Anesthetic.","authors":"Adriana Šturcová","doi":"10.1021/acs.jpcb.4c05176","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c05176","url":null,"abstract":"<p><p>The structural response of 1,2-dimyristoyl-<i>sn-</i>glycero-3-phosphatidylcholine (DMPC)/water bilayers to addition and subsequent solvation of a small amphiphilic molecule - an anesthetic benzyl alcohol - was studied by means of solid-state NMR (²H NMR, ³¹P NMR) spectroscopy and low-angle X-ray diffraction. The sites of binding of this solute molecule within the bilayer were determined - the solute was shown to partition between several sites in the bilayer and the equilibrium was shown to be dynamic and dependent on the level of hydration and temperature. At the same time, it was shown that solubilization of benzyl alcohol reached a solubility limit and was terminated when the ordering profile of DMPC hydrocarbon chains adopted finite limiting values throughout the whole chain. Such findings were made probably for the first time for any lipid bilayer system and possibly have more general implications for dissolution of other small-molecule amphiphilic solutes in lipid bilayer systems other than DMPC. The limit to the hydrocarbon chain profile is probably a more general property and corresponds to the balance of intrabilayer and interbilayer forces established in combination with the elastic properties of the bilayer system that still consists of one single phase just before the solute forms an excess phase. It is not necessary to quantify the contribution of each individual intrabilayer and interbilayer force acting within such a bilayer system. A model of the dependence of surface density of lipid chains on the chain segment order parameter was also developed - an empirical mathematical model based on experimental data was derived and it was proposed to represent a relationship between intrinsic bilayer forces and bilayer deformation characteristics and might be proven to be of more general significance in the future.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035370","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":"Flexible Tail of Antimicrobial Peptide PGLa Facilitates Water Pore Formation in Membranes.","authors":"Chunsuo Tian, Xuyang Liu, Yuelei Hao, Haohao Fu, Xueguang Shao, Wensheng Cai","doi":"10.1021/acs.jpcb.4c06190","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c06190","url":null,"abstract":"<p><p>PGLa, an antimicrobial peptide (AMP), primarily exerts its antibacterial effects by disrupting bacterial cell membrane integrity. Previous theoretical studies mainly focused on the binding mechanism of PGLa with membranes, while the mechanism of water pore formation induced by PGLa peptides, especially the role of structural flexibility in the process, remains unclear. In this study, using all-atom simulations, we investigated the entire process of membrane deformation caused by the interaction of PGLa with an anionic cell membrane composed of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG). Using a deep learning-based key intermediate identification algorithm, we found that the C-terminal tail plays a crucial role for PGLa insertion into the membrane, and that with its assistance, a variety of water pores formed inside the membrane. Mutation of the tail residues revealed that, in addition to electrostatic and hydrophobic interactions, the flexibility of the tail residues is crucial for peptide insertion and pore formation. The full extension of these flexible residues enhances peptide-peptide and peptide-membrane interactions, guiding the transmembrane movement of PGLa and the aggregation of PGLa monomers within the membrane, ultimately leading to the formation of water-filled pores in the membrane. Overall, this study provides a deep understanding of the transmembrane mechanism of PGLa and similar AMPs, particularly elucidating for the first time the importance of C-terminal flexibility in both insertion and oligomerization processes.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027479","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}