Pub Date : 2024-11-07Epub Date: 2024-10-28DOI: 10.1021/acs.jpcb.4c04895
Thanh T Lai, Charles L Brooks
The Lipari-Szabo generalized order parameter probes the picosecond to nanosecond time scale motions of a protein and is useful for rationalizing a multitude of biological processes such as protein recognition and ligand binding. Although these fast motions are an important and intrinsic property of proteins, it remains unclear what simulation conditions are most suitable to reproduce methyl symmetry axis side chain order parameter data (Saxis2) from molecular dynamics simulations. In this study, we show that, while Saxis2 tends to converge within tens of nanoseconds, it is essential to run 10 to 20 replicas starting from configurations close to the experimental structure to obtain the best agreement with experimental Saxis2 values. Additionally, in a comparison of force fields, AMBER ff14SB outperforms CHARMM36m in accurately capturing these fast time scale motions, and we suggest that the origin of this performance gap is likely attributed to differences in side chain torsional parametrization and not due to differences in the global protein conformations sampled by the force fields. This study provides insight into obtaining accurate and reproducible Saxis2 values from molecular simulations and underscores the necessity of using replica simulations to compute equilibrium properties.
{"title":"Accuracy and Reproducibility of Lipari-Szabo Order Parameters From Molecular Dynamics.","authors":"Thanh T Lai, Charles L Brooks","doi":"10.1021/acs.jpcb.4c04895","DOIUrl":"10.1021/acs.jpcb.4c04895","url":null,"abstract":"<p><p>The Lipari-Szabo generalized order parameter probes the picosecond to nanosecond time scale motions of a protein and is useful for rationalizing a multitude of biological processes such as protein recognition and ligand binding. Although these fast motions are an important and intrinsic property of proteins, it remains unclear what simulation conditions are most suitable to reproduce methyl symmetry axis side chain order parameter data (<i>S</i><sub>axis</sub><sup>2</sup>) from molecular dynamics simulations. In this study, we show that, while <i>S</i><sub>axis</sub><sup>2</sup> tends to converge within tens of nanoseconds, it is essential to run 10 to 20 replicas starting from configurations close to the experimental structure to obtain the best agreement with experimental <i>S</i><sub>axis</sub><sup>2</sup> values. Additionally, in a comparison of force fields, AMBER ff14SB outperforms CHARMM36m in accurately capturing these fast time scale motions, and we suggest that the origin of this performance gap is likely attributed to differences in side chain torsional parametrization and not due to differences in the global protein conformations sampled by the force fields. This study provides insight into obtaining accurate and reproducible <i>S</i><sub>axis</sub><sup>2</sup> values from molecular simulations and underscores the necessity of using replica simulations to compute equilibrium properties.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491189","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}
Pub Date : 2024-11-07Epub Date: 2024-10-24DOI: 10.1021/acs.jpcb.4c05462
Zhinan Liu, Guicai Zhang, Rongkai Yuan, Xiang Wang
With the advancement of technologies for developing tight and shale reservoirs, nonionic surfactants have garnered significant attention due to their remarkable properties. The structure of these surfactants plays a crucial role in determining the characteristics of the oil-water interface, particularly influencing emulsification behavior and crude oil recovery. This study investigates the effect of varying the number of hydrophilic polar groups (n = 10, 20, 30, 50) in octylphenol polyoxyethylene ether (OP-n) on its adsorption behavior at the n-hexadecane-water interface using molecular dynamics simulation. The impact of these variations on interfacial properties was further analyzed through measurements of interfacial tension and observations of emulsion droplet morphology. The study results indicate that variations in the number of hydrophilic polar groups significantly affect interfacial properties. Increasing the number of hydrophilic polar groups led to a notable increase in the thickness of the n-hexadecane or water phase, as well as the thickness of the water or oil layer and the surfactant layer. Moreover, when the number of hydrophilic polar groups reached 20, the OP-n molecules exhibited a more curled conformation at the interface, enhancing their ability to encapsulate water and resulting in a decrease in the diffusion coefficient of the molecules in each phase. Additionally, interfacial tension was found to be positively correlated with the number of hydrophilic polar groups and remained unchanged beyond a certain emulsion diameter. This study provides a theoretical basis and reference data for optimizing surfactant structures to improve crude oil recovery.
{"title":"Hydrophilic Chain Length for Octylphenol Polyoxyethylene Ether Adsorption at the <i>n</i>-Hexadecane-Water Interface: Theoretical and Experimental Study.","authors":"Zhinan Liu, Guicai Zhang, Rongkai Yuan, Xiang Wang","doi":"10.1021/acs.jpcb.4c05462","DOIUrl":"10.1021/acs.jpcb.4c05462","url":null,"abstract":"<p><p>With the advancement of technologies for developing tight and shale reservoirs, nonionic surfactants have garnered significant attention due to their remarkable properties. The structure of these surfactants plays a crucial role in determining the characteristics of the oil-water interface, particularly influencing emulsification behavior and crude oil recovery. This study investigates the effect of varying the number of hydrophilic polar groups (<i>n</i> = 10, 20, 30, 50) in octylphenol polyoxyethylene ether (OP-<i>n</i>) on its adsorption behavior at the <i>n</i>-hexadecane-water interface using molecular dynamics simulation. The impact of these variations on interfacial properties was further analyzed through measurements of interfacial tension and observations of emulsion droplet morphology. The study results indicate that variations in the number of hydrophilic polar groups significantly affect interfacial properties. Increasing the number of hydrophilic polar groups led to a notable increase in the thickness of the <i>n</i>-hexadecane or water phase, as well as the thickness of the water or oil layer and the surfactant layer. Moreover, when the number of hydrophilic polar groups reached 20, the OP-<i>n</i> molecules exhibited a more curled conformation at the interface, enhancing their ability to encapsulate water and resulting in a decrease in the diffusion coefficient of the molecules in each phase. Additionally, interfacial tension was found to be positively correlated with the number of hydrophilic polar groups and remained unchanged beyond a certain emulsion diameter. This study provides a theoretical basis and reference data for optimizing surfactant structures to improve crude oil recovery.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491198","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}
Pub Date : 2024-11-07Epub Date: 2024-10-28DOI: 10.1021/acs.jpcb.4c04619
Seishi Shimizu, Nobuyuki Matubayasi
The solubility of hydrophobic solutes increases dramatically with the temperature when hydrotropes are added to water. In this paper, the mechanism of this well-known observation will be explained via statistical thermodynamics through (i) enhanced enthalpy-hydrotrope number correlation locally (around the solute) that promotes the temperature dependence and (ii) hydrotrope self-association in the bulk solution that suppresses the temperature dependence. The contribution from (i), demonstrated to be dominant for urea as a hydrotrope, signifies the weakening of interaction energies around the solute (local) than in the bulk that accompanies incoming hydrotrope molecules. Thus, studying hydrotropic solubilization along the temperature and hydrotrope concentration provides complementary information on the local-bulk difference: the local accumulation of hydrotropes around the solute, driven by the enhanced local hydrotrope self-association, is also accompanied by the overall local weakening of energetic interactions, reflecting the fluctuational nature of hydrotrope association and the mediating role of water molecules.
{"title":"Temperature Dependence of Hydrotropy.","authors":"Seishi Shimizu, Nobuyuki Matubayasi","doi":"10.1021/acs.jpcb.4c04619","DOIUrl":"10.1021/acs.jpcb.4c04619","url":null,"abstract":"<p><p>The solubility of hydrophobic solutes increases dramatically with the temperature when hydrotropes are added to water. In this paper, the mechanism of this well-known observation will be explained via statistical thermodynamics through (i) enhanced enthalpy-hydrotrope number correlation locally (around the solute) that promotes the temperature dependence and (ii) hydrotrope self-association in the bulk solution that suppresses the temperature dependence. The contribution from (i), demonstrated to be dominant for urea as a hydrotrope, signifies the weakening of interaction energies around the solute (local) than in the bulk that accompanies incoming hydrotrope molecules. Thus, studying hydrotropic solubilization along the temperature and hydrotrope concentration provides complementary information on the local-bulk difference: the local accumulation of hydrotropes around the solute, driven by the enhanced local hydrotrope self-association, is also accompanied by the overall local weakening of energetic interactions, reflecting the fluctuational nature of hydrotrope association and the mediating role of water molecules.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520271","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}
Pub Date : 2024-11-07Epub Date: 2024-10-23DOI: 10.1021/acs.jpcb.4c04008
Fernando A Del Castillo, Nyssa T Emerson, Haw Yang
Accurately modeling plasmon-modified fluorescence is important for understanding and guiding the design of experimental nanostructures that reliably enhance fluorescence. They are of particular interest due to their potential to allow localized "hot spots" of high fluorescence enhancement in a reproducible manner. Given the increasingly prevalent use of the COMSOL Multiphysics software package for simulating these phenomena, we investigate its accuracy using an analytically tractable model consisting of a gold nanosphere interacting with either a plane wave or a radiating point dipole. COMSOL simulation results were compared with a formally exact analytical theory. It was found that simulation parameters commonly used for plane-wave scattering do not necessarily produce accurate results for the nanoparticle-plasmon-coupled dipole emission case. Instead, user-input adaptive meshing parameters were found to be helpful in achieving quantitative agreements between COMSOL and analytical theory results for plasmon-modified fluorescence. Our studies suggest convergence to analytically calculated values when a minimum of two additional user-input mesh elements separate the point-dipole position and the nanoparticle surface. This practical insight is expected to aid in the application of COMSOL simulations to planning and interpreting fluorescence modification experiments.
{"title":"Evaluating the Accuracy of the COMSOL-Based Finite-Element Method for Simulating Plasmon-Modified Fluorescence.","authors":"Fernando A Del Castillo, Nyssa T Emerson, Haw Yang","doi":"10.1021/acs.jpcb.4c04008","DOIUrl":"10.1021/acs.jpcb.4c04008","url":null,"abstract":"<p><p>Accurately modeling plasmon-modified fluorescence is important for understanding and guiding the design of experimental nanostructures that reliably enhance fluorescence. They are of particular interest due to their potential to allow localized \"hot spots\" of high fluorescence enhancement in a reproducible manner. Given the increasingly prevalent use of the COMSOL Multiphysics software package for simulating these phenomena, we investigate its accuracy using an analytically tractable model consisting of a gold nanosphere interacting with either a plane wave or a radiating point dipole. COMSOL simulation results were compared with a formally exact analytical theory. It was found that simulation parameters commonly used for plane-wave scattering do not necessarily produce accurate results for the nanoparticle-plasmon-coupled dipole emission case. Instead, user-input adaptive meshing parameters were found to be helpful in achieving quantitative agreements between COMSOL and analytical theory results for plasmon-modified fluorescence. Our studies suggest convergence to analytically calculated values when a minimum of two additional user-input mesh elements separate the point-dipole position and the nanoparticle surface. This practical insight is expected to aid in the application of COMSOL simulations to planning and interpreting fluorescence modification experiments.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491196","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}
Pub Date : 2024-11-07Epub Date: 2024-10-29DOI: 10.1021/acs.jpcb.4c05732
Solmaz Azimi, Emilio Gallicchio
We present receptor hopping and receptor swapping free energy estimation protocols based on the Alchemical Transfer Method (ATM) to model the binding selectivity of a set of ligands to two arbitrary receptors. The receptor hopping protocol, where a ligand is alchemically transferred from one receptor to another in one simulation, directly yields the ligand's binding selectivity free energy (BSFE) for the two receptors, which is the difference between the two individual binding free energies. In the receptor swapping protocol, the first ligand of a pair is transferred from one receptor to another while the second ligand is simultaneously transferred in the opposite direction. The receptor swapping free energy yields the differences in binding selectivity free energies of a set of ligands, which, when combined using a generalized DiffNet algorithm, yield the binding selectivity free energies of the ligands. We test these algorithms on host-guest systems and show that they yield results that agree with experimental data and are consistent with differences in absolute and relative binding free energies obtained by conventional methods. Preliminary applications to the selectivity analysis of molecular fragments binding to the trypsin and thrombin serine protease confirm the potential of the receptor swapping technology in structure-based drug discovery. The novel methodologies presented in this work are a first step toward streamlined and computationally efficient protocols for ligand selectivity optimization between mutants and homologous proteins.
{"title":"Binding Selectivity Analysis from Alchemical Receptor Hopping and Swapping Free Energy Calculations.","authors":"Solmaz Azimi, Emilio Gallicchio","doi":"10.1021/acs.jpcb.4c05732","DOIUrl":"10.1021/acs.jpcb.4c05732","url":null,"abstract":"<p><p>We present receptor hopping and receptor swapping free energy estimation protocols based on the Alchemical Transfer Method (ATM) to model the binding selectivity of a set of ligands to two arbitrary receptors. The receptor hopping protocol, where a ligand is alchemically transferred from one receptor to another in one simulation, directly yields the ligand's binding selectivity free energy (BSFE) for the two receptors, which is the difference between the two individual binding free energies. In the receptor swapping protocol, the first ligand of a pair is transferred from one receptor to another while the second ligand is simultaneously transferred in the opposite direction. The receptor swapping free energy yields the differences in binding selectivity free energies of a set of ligands, which, when combined using a generalized DiffNet algorithm, yield the binding selectivity free energies of the ligands. We test these algorithms on host-guest systems and show that they yield results that agree with experimental data and are consistent with differences in absolute and relative binding free energies obtained by conventional methods. Preliminary applications to the selectivity analysis of molecular fragments binding to the trypsin and thrombin serine protease confirm the potential of the receptor swapping technology in structure-based drug discovery. The novel methodologies presented in this work are a first step toward streamlined and computationally efficient protocols for ligand selectivity optimization between mutants and homologous proteins.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520269","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}
Pub Date : 2024-11-07Epub Date: 2024-10-28DOI: 10.1021/acs.jpcb.4c03759
Falk Wüstemann, Paul Zech, Robert Magerle
In atomic force microscopy experiments on fluid samples, a capillary bridge forms between the tip and the fluid, causing an attractive capillary force. Here, we present a computational model of the capillary interaction between a solid sphere and a coarse-grained Lennard-Jones fluid containing 10% antifreeze particles with an enlarged van der Waals radius. The capillary force acting on the sphere is obtained from the displacement of the sphere in a trap potential as the sphere is incrementally approached and then retracted from the fluid. This yields force-distance data similar to that obtained in atomic force microscopy experiments. We use this methodology to study the influence of the cutoff radius of the truncated Lennard-Jones potentials on the capillary force and its temperature dependence. The latter is found to scale with the critical temperature of the system. With the presented approach, the tip-sample interaction can be studied for a wide range of complex fluids, particle shapes, and force-probing schemes.
{"title":"Coarse-Grained MD Simulations of the Capillary Interaction between a Sphere and a Binary Fluid with Truncated Lennard-Jones Potentials.","authors":"Falk Wüstemann, Paul Zech, Robert Magerle","doi":"10.1021/acs.jpcb.4c03759","DOIUrl":"10.1021/acs.jpcb.4c03759","url":null,"abstract":"<p><p>In atomic force microscopy experiments on fluid samples, a capillary bridge forms between the tip and the fluid, causing an attractive capillary force. Here, we present a computational model of the capillary interaction between a solid sphere and a coarse-grained Lennard-Jones fluid containing 10% antifreeze particles with an enlarged van der Waals radius. The capillary force acting on the sphere is obtained from the displacement of the sphere in a trap potential as the sphere is incrementally approached and then retracted from the fluid. This yields force-distance data similar to that obtained in atomic force microscopy experiments. We use this methodology to study the influence of the cutoff radius of the truncated Lennard-Jones potentials on the capillary force and its temperature dependence. The latter is found to scale with the critical temperature of the system. With the presented approach, the tip-sample interaction can be studied for a wide range of complex fluids, particle shapes, and force-probing schemes.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520270","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}
Pub Date : 2024-11-07Epub Date: 2024-10-24DOI: 10.1021/acs.jpcb.4c05480
Kai Töpfer, Eric Boittier, Mike Devereux, Andrea Pasti, Peter Hamm, Markus Meuwly
Parametrizing energy functions for ionic systems can be challenging. Here, the total energy function for an eutectic system consisting of water, SCN-, K+ and acetamide is improved vis-a-vis experimentally measured properties. Given the importance of electrostatic interactions, two different types of models are considered: the first (model M0) uses atom-centered multipole whereas the other two (models M1 and M2) are based on fluctuating minimal distributed charges (fMDCM) that respond to geometrical changes of SCN-. The Lennard-Jones parameters of the anion are adjusted to best reproduce experimentally known hydration free energies and densities, which are matched to within a few percent for the final models irrespective of the electrostatic model. Molecular dynamics simulations of the eutectic mixtures with varying water content (between 0 and 100%) yield radial distribution functions and frequency correlation functions for the CN-stretch vibration. Comparison with experiments indicates that models based on fMDCM are considerably more consistent than those using multipoles. Computed viscosities from models M1 and M2 are within 30% of measured values and their change with increasing water content is consistent with experiments. This is not the case for model M0.
{"title":"Force Fields for Deep Eutectic Mixtures: Application to Structure, Thermodynamics and 2D-Infrared Spectroscopy.","authors":"Kai Töpfer, Eric Boittier, Mike Devereux, Andrea Pasti, Peter Hamm, Markus Meuwly","doi":"10.1021/acs.jpcb.4c05480","DOIUrl":"10.1021/acs.jpcb.4c05480","url":null,"abstract":"<p><p>Parametrizing energy functions for ionic systems can be challenging. Here, the total energy function for an eutectic system consisting of water, SCN<sup>-</sup>, K<sup>+</sup> and acetamide is improved vis-a-vis experimentally measured properties. Given the importance of electrostatic interactions, two different types of models are considered: the first (model <b>M0</b>) uses atom-centered multipole whereas the other two (models <b>M1</b> and <b>M2</b>) are based on fluctuating minimal distributed charges (fMDCM) that respond to geometrical changes of SCN<sup>-</sup>. The Lennard-Jones parameters of the anion are adjusted to best reproduce experimentally known hydration free energies and densities, which are matched to within a few percent for the final models irrespective of the electrostatic model. Molecular dynamics simulations of the eutectic mixtures with varying water content (between 0 and 100%) yield radial distribution functions and frequency correlation functions for the CN-stretch vibration. Comparison with experiments indicates that models based on fMDCM are considerably more consistent than those using multipoles. Computed viscosities from models <b>M1</b> and <b>M2</b> are within 30% of measured values and their change with increasing water content is consistent with experiments. This is not the case for model <b>M0</b>.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491197","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}
Enzymatic activity is regulated by various mechanisms to ensure biologically proper functions. Notable instances of such regulation in homodimeric enzymes include "all-of-the-sites activity" and "half-of-the-sites activity". The difference in these activities lies in whether one or both of the subunits are simultaneously active. Owing to its uniqueness, the mechanism of half-of-the-sites activity has been widely investigated. Consequently, structural asymmetry derived from cooperative motion is considered to induce half-of-the-sites activity. In contrast, recent investigations have suggested that subunit-intrinsic properties or structural fluctuation also induces structural asymmetry. Hence, the mechanism underlying half-of-the-sites activity has not been completely elucidated. Additionally, most previous studies have focused only on half-of-the-sites activity. Therefore, by comparing the structural and dynamical properties of two representative homodimers exhibiting all-of-the-sites and half-of-the-sites activities, respectively, we attempted to elucidate the mechanism of half-of-the-sites activity. Specifically, all-atom molecular dynamics simulations were applied to lysyl-tRNA synthetase and tyrosyl-tRNA synthetase. Our analysis revealed that structural fluctuation is sufficient to induce structural asymmetry in addition to the well-established factor of cooperative motion. Considering that structural fluctuation is a common characteristic of any enzyme, it could be a general factor in half-of-the-sites activity.
{"title":"Structural Fluctuation in Homodimeric Aminoacyl-tRNA Synthetases Induces Half-of-the-Sites Activity.","authors":"Yoshino Okamoto, Takunori Yasuda, Rikuri Morita, Yasuteru Shigeta, Ryuhei Harada","doi":"10.1021/acs.jpcb.4c05191","DOIUrl":"10.1021/acs.jpcb.4c05191","url":null,"abstract":"<p><p>Enzymatic activity is regulated by various mechanisms to ensure biologically proper functions. Notable instances of such regulation in homodimeric enzymes include \"all-of-the-sites activity\" and \"half-of-the-sites activity\". The difference in these activities lies in whether one or both of the subunits are simultaneously active. Owing to its uniqueness, the mechanism of half-of-the-sites activity has been widely investigated. Consequently, structural asymmetry derived from cooperative motion is considered to induce half-of-the-sites activity. In contrast, recent investigations have suggested that subunit-intrinsic properties or structural fluctuation also induces structural asymmetry. Hence, the mechanism underlying half-of-the-sites activity has not been completely elucidated. Additionally, most previous studies have focused only on half-of-the-sites activity. Therefore, by comparing the structural and dynamical properties of two representative homodimers exhibiting all-of-the-sites and half-of-the-sites activities, respectively, we attempted to elucidate the mechanism of half-of-the-sites activity. Specifically, all-atom molecular dynamics simulations were applied to lysyl-tRNA synthetase and tyrosyl-tRNA synthetase. Our analysis revealed that structural fluctuation is sufficient to induce structural asymmetry in addition to the well-established factor of cooperative motion. Considering that structural fluctuation is a common characteristic of any enzyme, it could be a general factor in half-of-the-sites activity.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491209","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}
Pub Date : 2024-11-07Epub Date: 2024-10-29DOI: 10.1021/acs.jpcb.4c03365
Emilia Tomaszewska, Artur Stępniak, Dominika Wróbel, Katarzyna Bednarczyk, Jan Maly, Małgorzata Krzyżowska, Grzegorz Celichowski, Jarosław Grobelny, Katarzyna Ranoszek-Soliwoda
This manuscript presents a comprehensive study on the quantification of modifier molecules adsorbed on gold nanoparticles (AuNPs) using two complementary techniques Ellman's method (UV-vis spectroscopy) and isothermal titration calorimetry (ITC). In this paper, we compare the feasibility of using the ITC technique and Ellman's method to study the interactions of mercaptosulfonate compounds (sodium mercaptoethanesulfonate, MES, and sodium mercaptoundecanesulfonate, MUS) with the surface of AuNPs of various sizes. The thermodynamic functions of the attachment of mercaptosulfonates to AuNPs were determined, revealing a linear relationship between the number of adsorbed molecules and the surface area of the nanoparticles. The amount of MES and MUS determined by Ellman's method (7 and 11 molecules per square nm, respectively) is more than twice that measured by the ITC technique (3 and 4 molecules per square nm, respectively). The slight differences in the adsorption of MES and MUS on the gold surface are due to differences in the carbon chain length of the ligand molecules. In the case of MES, the formation of the Au-S bond is the dominant stage of the adsorption process, whereas for MUS, the ordering process and self-assembly of molecules on the gold surface are dominant.
{"title":"Quantification of the Surface Coverage of Gold Nanoparticles with Mercaptosulfonates Using Isothermal Titration Calorimetry (ITC).","authors":"Emilia Tomaszewska, Artur Stępniak, Dominika Wróbel, Katarzyna Bednarczyk, Jan Maly, Małgorzata Krzyżowska, Grzegorz Celichowski, Jarosław Grobelny, Katarzyna Ranoszek-Soliwoda","doi":"10.1021/acs.jpcb.4c03365","DOIUrl":"10.1021/acs.jpcb.4c03365","url":null,"abstract":"<p><p>This manuscript presents a comprehensive study on the quantification of modifier molecules adsorbed on gold nanoparticles (AuNPs) using two complementary techniques Ellman's method (UV-vis spectroscopy) and isothermal titration calorimetry (ITC). In this paper, we compare the feasibility of using the ITC technique and Ellman's method to study the interactions of mercaptosulfonate compounds (sodium mercaptoethanesulfonate, MES, and sodium mercaptoundecanesulfonate, MUS) with the surface of AuNPs of various sizes. The thermodynamic functions of the attachment of mercaptosulfonates to AuNPs were determined, revealing a linear relationship between the number of adsorbed molecules and the surface area of the nanoparticles. The amount of MES and MUS determined by Ellman's method (7 and 11 molecules per square nm, respectively) is more than twice that measured by the ITC technique (3 and 4 molecules per square nm, respectively). The slight differences in the adsorption of MES and MUS on the gold surface are due to differences in the carbon chain length of the ligand molecules. In the case of MES, the formation of the Au-S bond is the dominant stage of the adsorption process, whereas for MUS, the ordering process and self-assembly of molecules on the gold surface are dominant.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542924","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}
Pub Date : 2024-11-07Epub Date: 2024-10-23DOI: 10.1021/acs.jpcb.4c04209
Souvik Chakraborty, Jia Min Phang, Shikhar Gupta, ChunSong Chua, Mary Moran, Ross Strand, Marco Klähn
Atomistic models of the plasma membrane of the pathogenic mold Aspergillus niger are developed. These models are described with an empirical molecular mechanical (MM) force field in combination with molecular dynamics (MD) simulations. The solvated plasma membrane models are brought into contact with 35 small organic compounds to observe their impact on a variety of membrane properties. All compounds are added at a constant total mass of 1% of the membrane mass. In addition, the ability of these compounds to inhibit the pathogenic cell growth of mold has been measured. Diffusion of compounds into the membrane model is readily observed during MD simulations. Changes in membrane properties found in simulations are not found to correlate with measured antifungal activities of compounds, suggesting that MD simulations of up to 1 μs are not sufficiently long to adequately describe compound-induced membrane disruption. However, properties related to the position and orientation of compounds relative to the membrane surface as well as hydrogen bonds formed between the compounds and the membrane show clear trends that correlate well with measured activities. A combination of these properties enables an activity prediction of compounds in good agreement with measurements. Activity is found predominantly for compounds that can be decomposed into a single continuous hydrophobic and hydrophilic moiety. Such active compounds can be energetically inserted most favorably into the membrane. These insertions destabilize the membrane by disrupting the internal membrane hydrogen bond network and by sliding between neighboring lipids, thereby separating them.
{"title":"Predicting the Antifungal Activity of Small Organic Compounds on <i>Aspergillus niger</i> Mold using Molecular Dynamics Simulations.","authors":"Souvik Chakraborty, Jia Min Phang, Shikhar Gupta, ChunSong Chua, Mary Moran, Ross Strand, Marco Klähn","doi":"10.1021/acs.jpcb.4c04209","DOIUrl":"10.1021/acs.jpcb.4c04209","url":null,"abstract":"<p><p>Atomistic models of the plasma membrane of the pathogenic mold <i>Aspergillus niger</i> are developed. These models are described with an empirical molecular mechanical (MM) force field in combination with molecular dynamics (MD) simulations. The solvated plasma membrane models are brought into contact with 35 small organic compounds to observe their impact on a variety of membrane properties. All compounds are added at a constant total mass of 1% of the membrane mass. In addition, the ability of these compounds to inhibit the pathogenic cell growth of mold has been measured. Diffusion of compounds into the membrane model is readily observed during MD simulations. Changes in membrane properties found in simulations are not found to correlate with measured antifungal activities of compounds, suggesting that MD simulations of up to 1 μs are not sufficiently long to adequately describe compound-induced membrane disruption. However, properties related to the position and orientation of compounds relative to the membrane surface as well as hydrogen bonds formed between the compounds and the membrane show clear trends that correlate well with measured activities. A combination of these properties enables an activity prediction of compounds in good agreement with measurements. Activity is found predominantly for compounds that can be decomposed into a single continuous hydrophobic and hydrophilic moiety. Such active compounds can be energetically inserted most favorably into the membrane. These insertions destabilize the membrane by disrupting the internal membrane hydrogen bond network and by sliding between neighboring lipids, thereby separating them.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491205","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}