The Journal of Physical Chemistry B最新文献

{"title":"Molecular Dynamics Investigation into the Stability of KRas and CRaf Multimeric Complexes.","authors":"Chongli Geng, Juan Zeng, Xianming Deng, Fei Xia, Xin Xu","doi":"10.1021/acs.jpcb.4c08767","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c08767","url":null,"abstract":"<p><p>In the Ras/Raf/MAPK signaling pathway, Ras and Raf proteins interact synergistically to form a tetrameric complex. NMR experiments have demonstrated that Ras dimerizes in solution and binds stably to Raf, forming Ras·Raf complexes. In this study, we constructed the ternary and quaternary complexes of KRas and CRaf based on crystal structures, denoted as (KRas)₂·CRaf and (KRas)₂·(CRaf)₂, respectively. Molecular dynamics (MD) simulations were performed to investigate the stability of these complexes, while hydrogen bonds as well as salt bridges formed at the protein-protein interaction interfaces were analyzed based on simulation trajectories. The results revealed that the KRas·CRaf complex is more stable in explicit solvent compared with the KRas dimer. Formation of the stable quaternary complex (KRas)₂·(CRaf)₂ might be attributed to the association of two binary KRas·CRaf complexes. Additionally, MD simulations of the KRasG12D·CRaf complex revealed a stable and extended binding site at the KRas-CRaf interaction interface. This binding site was identified as a potential therapeutic target to block abnormal signal transmission in the pathway.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690515","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":"Exploring Catechol Binding to Laccase with Insights into Enzyme Dynamics for Biosensing Applications.","authors":"Anushka Biswas, Mithun Radhakrishna","doi":"10.1021/acs.jpcb.4c08556","DOIUrl":"10.1021/acs.jpcb.4c08556","url":null,"abstract":"<p><p>There is growing interest in using enzymatic sensors and bioreactors for detecting and removing toxic compounds. Phenolic pollutants like catechol are a major concern, and laccase, a versatile oxidase, has been widely employed for catechol degradation due to its strong binding affinity. In this study, we reconstruct the binding mechanism of catechol to laccase from the white-rot fungus Trametes versicolor using molecular dynamics simulations, free-energy calculations, Markov state modeling (MSM), and transition path theory (TPT). Our approach identifies five distinct macrostates, offering atomic-level insights into the structural and energetic landscape of the laccase-catechol interaction. Critical transition states and intermediates were characterized, emphasizing the role of the active site loop (A161-F162-P163-L164) and a gate mechanism involving neighboring residues. TPT analysis further quantified transitions among macrostates, revealing two dominant pathways that guide catechol from the unbound state to the active site through sequential and cooperative conformational changes.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699116","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":"How Does an Anti-Cancer Peptide Passively Permeate the Plasma Membrane of a Cancer Cell and Not a Normal Cell?","authors":"Alfredo E. Cardenas,&nbsp;Ehud Neumann,&nbsp;Yang Sung Sohn,&nbsp;Taylor Hays,&nbsp;Rachel Nechushtai,&nbsp;Lauren J. Webb and Ron Elber*,&nbsp;","doi":"10.1021/acs.jpcb.5c0068010.1021/acs.jpcb.5c00680","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c00680https://doi.org/10.1021/acs.jpcb.5c00680","url":null,"abstract":"<p >Passive and targeted delivery of peptides to cells and organelles is a fundamental biophysical process controlled by membranes surrounding biological compartments. Embedded proteins, phospholipid composition, and solution conditions contribute to targeted transport. An anticancer peptide, NAF-1^44–67, permeates to cancer cells but not to normal cells. The mechanism of this selectivity is of significant interest. However, the complexity of biomembranes makes pinpointing passive targeting mechanisms difficult. To dissect contributions to selective transport by membrane components, we constructed simplified phospholipid vesicles as plasma membrane (PM) models of cancer and normal cells and investigated NAF-1^44–67 permeation computationally and experimentally. We use atomically detailed simulations with enhanced sampling techniques to study kinetics and thermodynamics of the interaction. Experimentally, we study the interaction of the peptide with large and giant unilamellar vesicles. The large vesicles were investigated with fluorescence spectroscopy and the giant vesicles with confocal microscopy. Peptide permeation across a model of cancer PM is more efficient than permeation across a PM model of normal cells. The investigations agree on the mechanism of selectivity, which consists of three steps: (i) early electrostatic attraction of the peptide to the negatively charged membrane, (ii) the penetration of the peptide hydrophobic N-terminal segment into the lipid bilayer, and (iii) exploiting short-range electrostatic forces to create a defect in the membrane and complete the permeation process. The first step is kinetically less efficient in a normal membrane with fewer negatively charged phospholipids. The model of a normal membrane is less receptive to defect creation in the third step.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"129 13","pages":"3408–3419 3408–3419"},"PeriodicalIF":2.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758864","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":"Exciton Transfer Simulations in a Light-Harvesting 2 Complex Reveal the Transient Delocalization Mechanism.","authors":"David S Hoffmann, Philipp M Dohmen, Monja Sokolov, Ulrich Kleinekathöfer, Marcus Elstner","doi":"10.1021/acs.jpcb.5c00320","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c00320","url":null,"abstract":"<p><p>The striking efficiency of exciton transfer in light-harvesting (LH) complexes has remained a topic of debate since the revision of the long-held role of electronic coherences. To address this issue, we have developed a neural network for the pigments in the LH2 complex of <i>Rhodospirillum molischianum</i> that allows nonadiabatic molecular dynamic (NAMD) simulations of exciton transfer in a coupled quantum mechanical/molecular mechanics (QM/MM) embedding. The calculated exciton occupations are averaged over hundreds of trajectories, each lasting several picoseconds. We have obtained transitions within the B800 and B850 rings that agree well with the experimental results, indicating an incoherent hopping process in the B800 ring and a more delocalized transfer in the B850 subsystem. The reorganization energies and excitonic couplings are comparable to each other, indicating that the \"transient delocalization\" transport model is the underlying cause of the highly efficient exciton transport in the B850 ring. This phenomenon can be attributed to a localized exciton that shows occasional large delocalization events. Our results indicate that the reason for the striking efficiency is the unusual electronic property of bacteriochlorophyll, manifested in minimal inner and outer sphere reorganization energies.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699115","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":"Exciton Transfer Simulations in a Light-Harvesting 2 Complex Reveal the Transient Delocalization Mechanism","authors":"David S. Hoffmann,&nbsp;Philipp M. Dohmen,&nbsp;Monja Sokolov,&nbsp;Ulrich Kleinekathöfer and Marcus Elstner*,&nbsp;","doi":"10.1021/acs.jpcb.5c0032010.1021/acs.jpcb.5c00320","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c00320https://doi.org/10.1021/acs.jpcb.5c00320","url":null,"abstract":"<p >The striking efficiency of exciton transfer in light-harvesting (LH) complexes has remained a topic of debate since the revision of the long-held role of electronic coherences. To address this issue, we have developed a neural network for the pigments in the LH2 complex of <i>Rhodospirillum molischianum</i> that allows nonadiabatic molecular dynamic (NAMD) simulations of exciton transfer in a coupled quantum mechanical/molecular mechanics (QM/MM) embedding. The calculated exciton occupations are averaged over hundreds of trajectories, each lasting several picoseconds. We have obtained transitions within the B800 and B850 rings that agree well with the experimental results, indicating an incoherent hopping process in the B800 ring and a more delocalized transfer in the B850 subsystem. The reorganization energies and excitonic couplings are comparable to each other, indicating that the “transient delocalization” transport model is the underlying cause of the highly efficient exciton transport in the B850 ring. This phenomenon can be attributed to a localized exciton that shows occasional large delocalization events. Our results indicate that the reason for the striking efficiency is the unusual electronic property of bacteriochlorophyll, manifested in minimal inner and outer sphere reorganization energies.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"129 13","pages":"3345–3365 3345–3365"},"PeriodicalIF":2.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758874","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":"Development of SAFT-Based Coarse-Grained Models of Carbon Dioxide and Nitrogen","authors":"Alexandros Chremos*,&nbsp;William P. Krekelberg,&nbsp;Harold W. Hatch,&nbsp;Daniel W. Siderius,&nbsp;Nathan A. Mahynski and Vincent K. Shen,&nbsp;","doi":"10.1021/acs.jpcb.5c0053610.1021/acs.jpcb.5c00536","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c00536https://doi.org/10.1021/acs.jpcb.5c00536","url":null,"abstract":"<p >We develop coarse-grained models for carbon dioxide (CO₂) and nitrogen (N₂) that capture the vapor–liquid equilibria of both their single components and their binary mixtures over a wide range of temperatures and pressures. To achieve this, we used an equation of state (EoS), namely Statistical Associating Fluid Theory (SAFT), which utilizes a molecular-based algebraic description of the free energy of chain fluids. This significantly accelerates the exploration of the parameter space, enabling the development of coarse-grained models that provide an optimal description of the macroscopic experimental data. SAFT creates models of fluids by chaining together spheres, which represent coarse-grained parts of a molecule. The result is a series of fitted parameters, such as bead size, bond length, and interaction strengths, that seem amenable to molecular simulation. However, only a limited set of models can be directly implemented in a particle-based simulation; this is predominantly due to how SAFT handles overlap between bonded monomers with parameters that do not translate to physical features, such as bond length. To translate such parameters to bond lengths in a coarse-grained force-field, we performed Wang–Landau transition-matrix Monte Carlo (WL-TMMC) simulations in the grand canonical ensemble on homonuclear fused two-segment Mie models and evaluated the phase behavior at different bond lengths. In the spirit of the law of corresponding states, we found that a force field, which matches SAFT predictions, can be derived by rescaling length and energy scales based on ratios of critical point properties of simulations and experiments. The phase behavior of CO₂ and N₂ mixtures was also investigated. Overall, we found excellent agreement over a wide range of temperatures and pressures in pure components and mixtures, similar to TraPPE CO₂ and N₂ models. Our proposed approach is the first step to establishing a more robust bridge between SAFT and molecular simulation modeling.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"129 13","pages":"3443–3453 3443–3453"},"PeriodicalIF":2.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jpcb.5c00536","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of SAFT-Based Coarse-Grained Models of Carbon Dioxide and Nitrogen.","authors":"Alexandros Chremos, William P Krekelberg, Harold W Hatch, Daniel W Siderius, Nathan A Mahynski, Vincent K Shen","doi":"10.1021/acs.jpcb.5c00536","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c00536","url":null,"abstract":"<p><p>We develop coarse-grained models for carbon dioxide (CO₂) and nitrogen (N₂) that capture the vapor-liquid equilibria of both their single components and their binary mixtures over a wide range of temperatures and pressures. To achieve this, we used an equation of state (EoS), namely Statistical Associating Fluid Theory (SAFT), which utilizes a molecular-based algebraic description of the free energy of chain fluids. This significantly accelerates the exploration of the parameter space, enabling the development of coarse-grained models that provide an optimal description of the macroscopic experimental data. SAFT creates models of fluids by chaining together spheres, which represent coarse-grained parts of a molecule. The result is a series of fitted parameters, such as bead size, bond length, and interaction strengths, that seem amenable to molecular simulation. However, only a limited set of models can be directly implemented in a particle-based simulation; this is predominantly due to how SAFT handles overlap between bonded monomers with parameters that do not translate to physical features, such as bond length. To translate such parameters to bond lengths in a coarse-grained force-field, we performed Wang-Landau transition-matrix Monte Carlo (WL-TMMC) simulations in the grand canonical ensemble on homonuclear fused two-segment Mie models and evaluated the phase behavior at different bond lengths. In the spirit of the law of corresponding states, we found that a force field, which matches SAFT predictions, can be derived by rescaling length and energy scales based on ratios of critical point properties of simulations and experiments. The phase behavior of CO₂ and N₂ mixtures was also investigated. Overall, we found excellent agreement over a wide range of temperatures and pressures in pure components and mixtures, similar to TraPPE CO₂ and N₂ models. Our proposed approach is the first step to establishing a more robust bridge between SAFT and molecular simulation modeling.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672884","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":"Mechanistic Investigation of Green Fluorescent Protein Acquiring Energy for Emitting Light: A Theoretical Study.","authors":"Shuangqi Pi, Deping Hu, Ya-Jun Liu","doi":"10.1021/acs.jpcb.4c08330","DOIUrl":"10.1021/acs.jpcb.4c08330","url":null,"abstract":"<p><p>Green fluorescent protein (GFP) is famous for noninvasively observing the internal biological processes of cells and organisms, revolutionizing the field of cell biology. GFP was first discovered in jellyfish <i>Aequorea victoria</i> (<i>AV</i>). The GFP bioluminescence (BL) in <i>AV</i> can be divided into three stages: the first singlet excited state coelenteramide (S₁-CTD) is formed in aequorin; GFP acquires energy from S₁-CTD via an energy transfer (ET) process; and GFP emits green light. The first and final stages have been well studied, whereas the detailed mechanism of the second stage remains unclear, with only sporadic experimental evidence. The purpose of this study is to clarify how GFP acquires energy before emitting green light in <i>AV</i>. Through protein-protein docking, molecular dynamics simulations, and combined quantum mechanics and molecular mechanics calculations, we demonstrate that the ET process occurs via the Förster resonance energy transfer (FRET) mechanism. The calculated FRET rate is faster than the radiative and nonradiative decay ones of S₁-CTD, which means the ET process can occur efficiently. Additionally, the calculated fluorescence quantum yield explains the experimentally observed BL enhancement after the ET. This is the first theoretical report on the ET mechanism in BL. This study not only clearly interprets how GFP acquires energy for emitting light but also helps to understand the ET mechanism in other bioluminescent systems and sheds new light on bioluminescence resonance energy transfer.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"2925-2933"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571569","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":"Another Possible Rationale for Foam Stability: The Quantity and Strength of Hydrogen Bonds at the Gas-Liquid Interface.","authors":"Bao Xiao, Tianyu Liu, Dongdong Wang, Lei Tang, Lihua Zhou, Shaohua Gou","doi":"10.1021/acs.jpcb.4c08131","DOIUrl":"10.1021/acs.jpcb.4c08131","url":null,"abstract":"<p><p>This study examines the foams generated by three surfactants: sodium dodecyl sulfate (SDS), sodium dodecylbenzenesulfonate (SDBS), and sodium lauryl polyoxyethylene ether sulfate (AES). By analyzing the hydrogen bond at the gas-liquid interface, the research provides novel insights into the mechanisms by which surfactants stabilize foams. Surfactants adsorb at the gas-liquid interface, establishing hydrogen bonds with water molecules while simultaneously retarding the structural relaxation of water-water hydrogen bonds within the hydration layer. This phenomenon can impede drainage during the surface tension drainage phase. Surfactants that readily form hydrogen bonds with water are more likely to adsorb at the gas-liquid interface, thereby enhancing the foam stability. The presence of robust hydrogen bonds and the frequent reconstruction of these bonds contribute to the establishment of a stable hydrogen bond network, which can reinforce the gas-liquid film and potentially augment its elasticity, enabling it to better withstand external perturbations. Although the Marangoni effect typically promotes bubble coalescence, a stable hydrogen bond network may mitigate this process.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"3083-3093"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575628","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":"Multiblock Copolymers at Liquid-Liquid Interfaces: Effect of the Block Sequence on Interfacial Tension and Polymer Conformation.","authors":"Aldo Vásquez-Briceño, Gustavo R Pérez-Lemus, Julio C Armas-Pérez, Abelardo Ramírez-Hernández","doi":"10.1021/acs.jpcb.4c07448","DOIUrl":"10.1021/acs.jpcb.4c07448","url":null,"abstract":"<p><p>Block copolymers of amphiphilic nature represent a distinctive class of macromolecules that have been extensively studied due to their intriguing surface-active properties. Their ability to reduce interfacial tension and create disperse phases, such as emulsions, has made them crucial in industries that rely on the interfacial effects of these molecules. Experimental and computational studies have reported the effects of changing various properties associated with the polymeric chains including stiffness, molecular weight, and other structural attributes. In this work, extensive molecular simulations were performed to understand how the sequence of an AB multiblock copolymer impacts the interfacial tension between two immiscible liquids. To efficiently explore a range of surface concentration values and four different block copolymer sequences, a coarse-grained model was employed. Simulation results indicate that at a fixed composition, block sequence has a strong effect on the rate of interfacial tension reduction as polymer surface concentration increases. Of all studied sequences, the alternating sequence was able to greatly reduce the interfacial tension at low surface concentrations, whereas pentablock and triblock sequences were able to reduce it even more than the alternating sequence, but it required a higher polymer surface concentration to achieve this. To correlate polymer conformations with interfacial effects, several structural descriptors were computed to quantify the conformations adopted by the macromolecules at the interface.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"3041-3052"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555370","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}