The Journal of Physical Chemistry B最新文献

{"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}

{"title":"Multiscale Simulations and Profiling of Human Thymidine Phosphorylase Mutations: Insights into Structural, Dynamics, and Functional Impacts in Mitochondrial Neurogastrointestinal Encephalopathy.","authors":"Khushboo Bhagat, Amar Jeet Yadav, Aditya K Padhi","doi":"10.1021/acs.jpcb.5c00771","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c00771","url":null,"abstract":"<p><p>Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a rare metabolic disorder caused by missense mutations in the <i>TYMP</i> gene, leading to the loss of human thymidine phosphorylase (HTP) activity and subsequent mitochondrial dysfunction. Despite its well-characterized biochemical basis, the molecular mechanisms by which MNGIE-associated mutations alter HTP's structural stability, dynamics, and substrate (thymidine) binding remain unclear. In this study, we employ a multiscale computational approach, integrating AlphaFold2-based structural modeling, all-atom and coarse-grained molecular dynamics (MD) simulations, protein-ligand (HTP-thymidine) docking, HTP-thymidine complex simulations, binding free-energy landscape analysis, and systematic mutational profiling to investigate the impact of key MNGIE-associated mutations (R44Q, G145R, G153S, K222S, and E289A) on HTP function. Analyses of our long-duration multiscale simulations (comprising 9 μs coarse-grained, 1.2 μs all-atom apo HTP, and 1.2 μs HTP-thymidine complex MD simulations) and physicochemical properties reveal that while wild-type HTP maintains structural integrity and strong thymidine-binding affinity, MNGIE-associated mutations induce substantial destabilization, increased flexibility, and reduced enzymatic efficiency. Free-energy landscape analysis highlights a shift toward less stable conformational states in mutant HTPs, further supporting their functional impairment. Additionally, the G145R mutation introduces steric hindrance at the active site, preventing thymidine binding and causing off-site interactions. These findings not only provide fundamental insights into the physicochemical and dynamic alterations underlying HTP dysfunction in MNGIE but also establish a computational framework for guiding future experimental studies and the rational design of therapeutic interventions aimed at restoring HTP function.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661578","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":"Advanced Strategy for High-Performance A-D-A'-D-A Type Non-Fused Ring Electron Acceptors with Nitrogen Heterocyclic Cores.","authors":"Yang Jiang, Chuang Yao, Yezi Yang, Jinshan Wang","doi":"10.1021/acs.jpcb.5c00283","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c00283","url":null,"abstract":"<p><p>The development of nonfused ring electron acceptors (NFREAs) has garnered significant attention due to their simplified molecular design and cost-effectiveness. Recent advancements have pushed the power conversion efficiency (PCE) of NFREAs beyond 19%. Despite these advantages, most NFREAs adopt A-D-A structures, where the electron-donating core is typically a benzene ring substituted with fluorine or alkoxy groups. This design restricts the tunability of energy levels, and the selection of substituents for benzene rings as central units is relatively constrained, which hampers further optimization of material properties. In this work, we designed three A-D-A'-D-A structured fully NFREAs featuring distinct nitrogen heterocyclic cores: linear-shaped <b>TT</b>, star-shaped <b>TYT</b>, and quad-rotor-shaped <b>TTVP</b>. The nitrogen-containing aromatic units, typically strong electron-withdrawing groups, enable precise tuning of energy levels. Moreover, these electron-withdrawing cores enhance molecular rigidity, facilitating efficient π-π stacking and improving electron mobility. Although these NFREAs share identical π-bridges and terminal groups, their unique nitrogen heterocyclic cores exert divergent effects on photovoltaic performance. Theoretical calculations reveal that <b>TT</b> and <b>TTVP</b> exhibit higher electron affinity, greater absorption intensity, lower exciton binding energy, and higher electron mobility compared to the high-performance reference NFREA, TBT-26. Notably, <b>TTVP</b>, featuring an electron-withdrawing core and four terminal groups, exhibits exceptional electronic properties. It achieves the highest electron affinity, the narrowest bandgap of 1.76 eV, and a predicted electron mobility of 4.43 × 10^-4 cm² V^-1 s^-1, surpassing TBT-26. These findings underscore the potential of nitrogen heterocyclic cores in diversifying NFREA design and advancing the development of next-generation high-performance NFREAs.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"129 11","pages":"3109-3119"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661602","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":"Nickel-Dithiolene Cofactors as Electron Donors and Acceptors in Protein Hosts.","authors":"Georgia Polycarpou, Spiros S Skourtis","doi":"10.1021/acs.jpcb.4c08264","DOIUrl":"10.1021/acs.jpcb.4c08264","url":null,"abstract":"<p><p>Metal dithiolene compounds are attracting considerable attention in the field of molecular electronics, particularly as constituents of materials with high charge-carrier mobilities. Recent experiments on cable bacteria that perform centimeter-scale charge transport suggest that Ni-bis(dithiolene) cofactors are important components of the bacterial conductive network. Further, current-voltage experiments of cable-bacteria-conductive sheaths have measured high conductivity values as compared to other electron-transfer bacteria. An important question is how the Ni-bis(dithiolene) structures participating as electron donors/acceptors contribute to the high conductivity. Currently, the protein and cofactor structures of these bacterial networks are largely unknown. Given this limitation, in this work, we explore the more general question of how Ni-bis(dithiolene) molecules would perform as electron donor and acceptor centers in protein-mediated charge transfer. Our aim is to deduce order-of-magnitude higher bounds for charge-transfer rates in such systems as a function of donor-acceptor distance, protein-bridge (amino acid) sequence, cofactor size, and redox state. These bounds are useful for predicting charge-transfer mechanisms and estimating rates in the absence of detailed structural information on protein wires that may use Ni-bis(dithiolene) redox cofactors. Our analysis is also relevant to the design of artificial Ni-bis(dithiolene) protein wires.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"2992-3006"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571570","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":"Water Transportation through Nano/Microsized Lipid Protocells with a Significant Deviation from the van't Hoff Osmotic Rule.","authors":"Shujiao Chen, Shuai Zhang, Qunhui Yuan, Wei Gan","doi":"10.1021/acs.jpcb.5c00133","DOIUrl":"10.1021/acs.jpcb.5c00133","url":null,"abstract":"<p><p>Osmotic pressure is known to be an important driving force that induces water transport through membranes, which is crucial for many biophysical processes. Here, we observed that under a relatively low osmotic pressure induced by sugars' protocells (vesicles) with a diameter of ∼110 nm barely shrank. However, NaCl and CaCl₂ at lower concentrations induced a rapid decrease in the vesicle size as evidence of water transportation through the membrane. An additional mechanical pressure resulting from the increase in interfacial tension of the lipid membrane was proposed to be the main driving force of this electrolyte-specific effect. These results indicate that osmotic pressure is not the only driving force of water transport in nano/microsized lipid protocells.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"3103-3108"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603059","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":"PCDTBT: Force Field Parameterization and Properties by Molecular Dynamics Simulation.","authors":"Konstantinos Kordos, Konstantinos Kaklamanis, Maria Andrea, Dimitrios G Papageorgiou","doi":"10.1021/acs.jpcb.4c08393","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c08393","url":null,"abstract":"<p><p>Conjugated polymers are indispensable building blocks in a variety of organic electronics applications such as solar cells, light-emitting diodes, and field-effect transistors. Poly[<i>N</i>-9'-heptadecanyl-2,7-carbazole-<i>alt</i>-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)] (PCDTBT) is a carbazole-benzothiadiazole-based copolymer with a donor-acceptor structure, consisting of electron-donating and electron-withdrawing subunits and featuring a low band gap. In this work, the General Amber Force Field is extended in two ways, specifically for modeling PCDTBT. First, a set of partial atomic charges is derived that mimic a long chain and adequately describe different conformations that may be encountered in a bulk environment. Second, torsional terms are reparametrized for all dihedral angles in the backbone via ab initio computations. Subsequently, a series of large-scale Molecular Dynamics simulations are employed to construct and equilibrate bulk ensembles of three PCDTBT oligomers using different starting conformations of the oligomer chains. Several structural properties are computed, namely mass density, chain stiffness (through persistence length and Kuhn segment length), and glass transition temperature. Our results are in good agreement with available literature data, demonstrating the suitability of the new parametrization.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668497","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":"<i>Ab Initio</i> Molecular Dynamics Simulations of Amino Acids and Their Ammonia-Based Analogues in Ammonia.","authors":"Henrik Niemöller, Johannes Ingenmey, Oldamur Hollóczki, Barbara Kirchner","doi":"10.1021/acs.jpcb.4c06751","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c06751","url":null,"abstract":"<p><p>α-Amino acids are the fundamental building blocks for complex molecular structures within the water-based biochemistry of Earth. In a hypothetical ammonia-based biochemistry, α-amino amidines may serve an equivalent role. In this study, we explore the basic properties of α-amino amidines in comparison to α-amino acids solvated in ammonia, utilizing <i>ab initio</i> molecular dynamics simulations. The investigation of the time-resolved molecular dipole moment reveals, in intricate detail, the relationship among the conformation, state, and magnitude of the dipole moment. Moreover, it allows for the tracking of proton-transfer reactions. In ammonia, α-amino acids tend to adopt an anionic state, with the zwitterionic state still being accessible. In contrast, the α-amino amidines remain neutral. Grotthuss diffusion is induced by the deprotonation of zwitterionic alanine. The charge transferred upon solvation serves as an indicator for the interaction strength between the solute and solvent. It is much stronger for α-amino acids, while, on average, the α-amino amidines exchange no charge with ammonia. The analyses reveal that in terms of structure, anionic α-amino acids behave very similarly to neutral α-amino amidines.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"129 11","pages":"3007-3017"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661598","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":"Prospective Evaluation of Structure-Based Simulations Reveal Their Ability to Predict the Impact of Kinase Mutations on Inhibitor Binding.","authors":"Sukrit Singh, Vytautas Gapsys, Matteo Aldeghi, David Schaller, Aziz M Rangwala, Jessica B White, Joseph P Bluck, Jenke Scheen, William G Glass, Jiaye Guo, Sikander Hayat, Bert L de Groot, Andrea Volkamer, Clara D Christ, Markus A Seeliger, John D Chodera","doi":"10.1021/acs.jpcb.4c07794","DOIUrl":"10.1021/acs.jpcb.4c07794","url":null,"abstract":"<p><p>Small molecule kinase inhibitors are critical in the modern treatment of cancers, evidenced by the existence of over 80 FDA-approved small-molecule kinase inhibitors. Unfortunately, intrinsic or acquired resistance, often causing therapy discontinuation, is frequently caused by mutations in the kinase therapeutic target. The advent of clinical tumor sequencing has opened additional opportunities for precision oncology to improve patient outcomes by pairing optimal therapies with tumor mutation profiles. However, modern precision oncology efforts are hindered by lack of sufficient biochemical or clinical evidence to classify each mutation as resistant or sensitive to existing inhibitors. Structure-based methods show promising accuracy in retrospective benchmarks at predicting whether a kinase mutation will perturb inhibitor binding, but comparisons are made by pooling disparate experimental measurements across different conditions. We present the first prospective benchmark of structure-based approaches on a blinded dataset of in-cell kinase inhibitor affinities to Abl kinase mutants using a NanoBRET reporter assay. We compare NanoBRET results to structure-based methods and their ability to estimate the impact of mutations on inhibitor binding (measured as ΔΔ<i>G</i>). Comparing physics-based simulations, Rosetta, and previous machine learning models, we find that structure-based methods accurately classify kinase mutations as inhibitor-resistant or inhibitor-sensitizing, and each approach has a similar degree of accuracy. We show that physics-based simulations are best suited to estimate ΔΔ<i>G</i> of mutations that are distal to the kinase active site. To probe modes of failure, we retrospectively investigate two clinically significant mutations poorly predicted by our methods, T315A and L298F, and find that starting configurations and protonation states significantly alter the accuracy of our predictions. Our experimental and computational measurements provide a benchmark for estimating the impact of mutations on inhibitor binding affinity for future methods and structure-based models. These structure-based methods have potential utility in identifying optimal therapies for tumor-specific mutations, predicting resistance mutations in the absence of clinical data, and identifying potential sensitizing mutations to established inhibitors.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"2882-2902"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575642","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":"Research at Predominately Undergraduate Institutions Published Recently in <i>The Journal of Physical Chemistry A, B,</i> and <i>C</i>.","authors":"George C Shields","doi":"10.1021/acs.jpcb.5c00978","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c00978","url":null,"abstract":"","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"129 11","pages":"2811-2814"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661604","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":"Research at Predominately Undergraduate Institutions Published Recently in The Journal of Physical Chemistry A, B, and C","authors":"George C. Shields*,&nbsp;","doi":"10.1021/acs.jpcb.5c0097810.1021/acs.jpcb.5c00978","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c00978https://doi.org/10.1021/acs.jpcb.5c00978","url":null,"abstract":"","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"129 11","pages":"2811–2814 2811–2814"},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143654316","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}