ACS Publications最新文献

{"title":"Accelerating Molecular Dynamics through Informed Resetting.","authors":"Jonathan R Church, Ofir Blumer, Tommer D Keidar, Leo Ploutno, Shlomi Reuveni, Barak Hirshberg","doi":"10.1021/acs.jctc.4c01238","DOIUrl":"10.1021/acs.jctc.4c01238","url":null,"abstract":"<p><p>We present a procedure for enhanced sampling of molecular dynamics simulations through informed stochastic resetting. Many phenomena, such as protein folding and crystal nucleation, occur over time scales inaccessible in standard simulations. We recently showed that stochastic resetting can accelerate molecular simulations that exhibit broad transition time distributions. However, standard stochastic resetting does not exploit any information about the reaction progress. For a model system and chignolin in explicit water, we demonstrate that an informed resetting protocol leads to greater accelerations than standard stochastic resetting in molecular dynamics and Metadynamics simulations. This is achieved by resetting only when a certain condition is met, e.g., when the distance from the target along the reaction coordinate is larger than some threshold. We use these accelerated simulations to infer important kinetic observables such as the unbiased mean first-passage time and direct transit time. For the latter, Metadynamics with informed resetting leads to speedups of 2-3 orders of magnitude over unbiased simulations with relative errors of only ∼35-70%. Our work significantly extends the applicability of stochastic resetting for enhanced sampling of molecular simulations.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"605-613"},"PeriodicalIF":5.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward Grid-Based Models for Molecular Association.","authors":"Hana Zupan, Bettina G Keller","doi":"10.1021/acs.jctc.4c01293","DOIUrl":"10.1021/acs.jctc.4c01293","url":null,"abstract":"<p><p>This paper presents a grid-based approach to model molecular association processes as an alternative to sampling-based Markov models. Our method discretizes the six-dimensional space of relative translation and orientation into grid cells. By discretizing the Fokker-Planck operator governing the system dynamics via the square-root approximation, we derive analytical expressions for the transition rate constants between grid cells. These expressions depend on geometric properties of the grid, such as the cell surface area and volume, which we provide. In addition, one needs only the molecular energy at the grid cell center, circumventing the need for extensive MD simulations and reducing the number of energy evaluations to the number of grid cells. The resulting rate matrix is closely related to the Markov state model transition matrix, offering insights into metastable states and association kinetics. We validate the accuracy of the model in identifying metastable states and binding mechanisms, though improvements are necessary to address limitations like ignoring bulk transitions and anisotropic rotational diffusion. The flexibility of this grid-based method makes it applicable to a variety of molecular systems and energy functions, including those derived from quantum mechanical calculations. The software package MolGri, which implements this approach, offers a systematic and computationally efficient tool for studying molecular association processes.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"614-628"},"PeriodicalIF":5.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solid-State Precipitation of Silver Nanoparticles Nucleated during Al Anodizing: Mechanism and Antibacterial Properties.","authors":"Teo Atz-Dick, Renato de Castro Valente, Thiago Vignoli Machado, Fabiana Horn, Luís F P Dick","doi":"10.1021/acsabm.4c01694","DOIUrl":"https://doi.org/10.1021/acsabm.4c01694","url":null,"abstract":"<p><p>This study presents an innovative approach to creating antibacterial aluminum surfaces by combining the antibacterial properties of silver nanoparticles (Ag NPs) with the nanoarchitecture of anodized aluminum oxide in one step. An Al-Ag alloy containing 10 wt % Ag was synthesized and anodized in 0.3 M oxalic acid. Ag NPs precipitated in the solid state during anodization, resulting in a porous nanocomposite structure. Comprehensive characterization using SEM, TEM, and EDS revealed a 43 μm thick oxide layer with uniformly distributed nanopores of approximately 100 nm in diameter. Ag NPs with diameters ranging from 2 to 14 nm precipitated dispersed on the surface, inside pores, and within the Al₂O₃ matrix. Antibacterial properties were evaluated against <i>Escherichia coli</i>. The anodized Al-Ag surface demonstrated robust antibacterial activity after short incubation times (up to 1 × 10⁸ CFU/ml after 3 h). The enhanced antibacterial properties are attributed to the optimal size and distribution of Ag NPs and the potential physical bactericidal effect of the nanoporous structure. This strategy for the precipitation of Ag NPs in the solid state could be used to fabricate high-touch surfaces in hospitals.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioaerosol Characterization with Vibrational Spectroscopy: Overcoming Fluorescence with Photothermal Infrared (PTIR) Spectroscopy.","authors":"Jia H Shi, Carlie J Poworoznek, Rebecca L Parham, Katherine R Kolozsvari, Nicole E Olson, Yao Xiao, Ziying Lei, Johnna A Birbeck, Stephen J Jacquemin, Judy A Westrick, Andrew P Ault","doi":"10.1021/acs.jpca.4c07848","DOIUrl":"https://doi.org/10.1021/acs.jpca.4c07848","url":null,"abstract":"<p><p>Aerosols containing biological material (i.e., bioaerosols) impact public health by transporting toxins, allergens, and diseases and impact the climate by nucleating ice crystals and cloud droplets. Single particle characterization of primary biological aerosol particles (PBAPs) is essential, as individual particle physicochemical properties determine their impacts. Vibrational spectroscopies, such as infrared (IR) or Raman spectroscopy, provide detailed information about the biological components within atmospheric aerosols but these techniques have traditionally been limited due to the diffraction limit of IR radiation (particles >10 μm) and fluorescence of bioaerosol components overwhelming the Raman signal. Herein, we use photothermal infrared spectroscopy (PTIR) to overcome these limitations and characterize individual PBAPs down to 0.18 μm. Both optical-PTIR (O-PTIR) and atomic force microscopy-PTIR (AFM-PTIR) were used to characterize bioaerosol particles generated from a cyanobacterial harmful algal bloom (cHAB) dominated by <i>Planktothrix agardhii</i>. PTIR spectra contained modes consistent with traditional Fourier transform infrared (FTIR) spectra for biological species, including amide I (1630-1700 cm^-1) and amide II (1530-1560 cm^-1). The fractions of particles containing biological materials were greater in supermicron particles (1.8-3.2 μm) than in submicron particles (0.18-0.32 and 0.56-1.0 μm) for aerosolized cHAB water. These results demonstrate the potential of both O-PTIR and AFM-PTIR for studying a range of bioaerosols with vibrational spectroscopy.</p>","PeriodicalId":59,"journal":{"name":"The Journal of Physical Chemistry A","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051068","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":"Refinement of the Sugar Puckering Torsion Potential in the AMBER DNA Force Field.","authors":"Marie Zgarbová, Jiří Šponer, Petr Jurečka","doi":"10.1021/acs.jctc.4c01100","DOIUrl":"10.1021/acs.jctc.4c01100","url":null,"abstract":"<p><p>The transition from B-DNA to A-DNA occurs in many protein-DNA interactions or in DNA/RNA hybrid duplexes, and thus plays a role in many important biomolecular processes that convey the biological function of DNA. However, the stability of A-DNA is severely underestimated in current AMBER force fields such as OL15, OL21 or bsc1, potentially leading to unstable or deformed protein-DNA complexes. In this study, we refine the deoxyribose dihedral potential to increase the stability of the north (N) puckering present in A-DNA. The new parameters, termed OL24, model A/B equilibrium in B-DNA duplexes in water in good agreement with nuclear magnetic resonance (NMR) experiment. They also improve the description of DNA/RNA hybrids and the transition of the DNA duplex to the A-form in concentrated ethanol solutions. These refinements significantly improve the modeling of protein-DNA complexes, increasing their structural stability and A-form population, while maintaining accurate representation of canonical B-DNA duplexes. Overall, the new parameters should allow more reliable modeling of the thermodynamic equilibrium between A- and B-DNA forms and the interactions of DNA with proteins.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"833-846"},"PeriodicalIF":5.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electronic Polarizability Tunes the Function of the Human Bestrophin 1 Cl^- Channel.","authors":"Linda X Phan, Aaron P Owji, Tingting Yang, Jason Crain, Mark S P Sansom, Stephen J Tucker","doi":"10.1021/acs.jctc.4c01039","DOIUrl":"10.1021/acs.jctc.4c01039","url":null,"abstract":"<p><p>Mechanisms of anion permeation within ion channels and nanopores remain poorly understood. Recent cryo-electron microscopy structures of the human bestrophin 1 Cl^- channel (hBest1) provide an opportunity to evaluate ion interactions predicted by molecular dynamics (MD) simulations against experimental observations. Here, we implement the fully polarizable force field AMOEBA in MD simulations on different conformations of hBest1. This force field models multipole moments up to the quadrupole. Using this approach, we model key biophysical properties of the channel that can only be simulated when electronic polarization is included in the molecular models and show that Cl^- permeation through the neck of the pore is achieved through hydrophobic solvation concomitant with partial ion dehydration. Furthermore, we demonstrate how such polarizable simulations can help determine the identity of ion-like densities within high-resolution cryo-EM structures and demonstrate that neglecting polarization places Cl^- at positions that do not correspond to their experimentally resolved location. Overall, our results demonstrate the importance of including electronic polarization in realistic and physically accurate models of biological systems, especially channels and pores that selectively permeate anions.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"933-942"},"PeriodicalIF":5.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nosé-Hoover Integrators at-a-Glance: Barostat Integration Has a Demonstrable Effect on Uniaxial Tension Results of Solid Materials.","authors":"Thomas J Barrett, Marilyn L Minus","doi":"10.1021/acs.jctc.4c01190","DOIUrl":"10.1021/acs.jctc.4c01190","url":null,"abstract":"<p><p>Molecular dynamics is a popular method for evaluating the tensile stress behaviors of many nanomaterials; however, few manuscripts include their thermostat and barostat damping parameters along with their methods. Here, we illustrate the demonstrable effect that barostat integration has on system dynamics during uniaxial testing under a Nosé-Hoover scheme. Three systems are tested: a 2D graphene sheet, a 3D continuous aluminum volume, and a 3D discontinuous polyvinyl alcohol volume. Isobaric-isothermal (NPT) and isochoric-isothermal (NVT) integration methods are intrinsically related, with high NPT barostat damping parameters converging on the NVT system. As a result, slight variations in barostat damping parameters may elicit different stress responses with higher damping parameters directly linked to increased levels of triaxial strain.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"517-529"},"PeriodicalIF":5.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data-Driven Improvement of Local Hybrid Functionals: Neural-Network-Based Local Mixing Functions and Power-Series Correlation Functionals.","authors":"Artur Wodyński, Kilian Glodny, Martin Kaupp","doi":"10.1021/acs.jctc.4c01503","DOIUrl":"10.1021/acs.jctc.4c01503","url":null,"abstract":"<p><p>Local hybrid functionals (LHs) use a real-space position-dependent admixture of exact exchange (EXX), governed by a local mixing function (LMF). The systematic construction of LMFs has been hampered over the years by a lack of exact physical constraints on their valence behavior. Here, we exploit a data-driven approach and train a new type of \"n-LMF\" as a relatively shallow neural network. The input features are of meta-GGA character, while the W4-17 atomization-energy and BH76 reaction-barrier test sets have been used for training. Simply replacing the widely used \"t-LMF\" of the LH20t functional by the n-LMF provides the LH24n-B95 functional. Augmented by DFT-D4 dispersion corrections, LH24n-B95-D4 remarkably improves the WTMAD-2 value for the large GMTKN55 test suite of general main-group thermochemistry, kinetics, and noncovalent interactions (NCIs) from 4.55 to 3.49 kcal/mol. As we found the limited flexibility of the B95c correlation functional to disfavor much further improvement on NCIs, we proceeded to replace it by an optimized B97c-type power-series expansion. This gives the LH24n functional. LH24n-D4 gives a WTMAD-2 value of 3.10 kcal/mol, the so far lowest value of a rung 4 functional in self-consistent calculations. The new functionals perform moderately well for organometallic transition-metal energetics while leaving room for further data-driven improvements in that area. Compared to complete neural-network functionals like DM21, the present more tailored approach to train just the LMF in a flexible but well-defined human-designed LH functional retains the possibility of graphical LMF analyses to gain deeper understanding. We find that both the present n-LMF and the recent x-LMF suppress the so-called gauge problem of local hybrids without adding a calibration function as required for other LMFs. LMF plots show that this can be traced back to large LMF values in the small-density region between the interacting atoms in NCIs for n- and x-LMFs and low values for the t-LMF. We also find that the trained n-LMF has relatively large values in covalent bonds without deteriorating binding energies. The current approach enables fast and efficient routine self-consistent calculations using n-LMFs in Turbomole.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"762-775"},"PeriodicalIF":5.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accurate QM/MM Molecular Dynamics for Periodic Systems in GPU4PySCF with Applications to Enzyme Catalysis.","authors":"Chenghan Li, Garnet Kin-Lic Chan","doi":"10.1021/acs.jctc.4c01698","DOIUrl":"10.1021/acs.jctc.4c01698","url":null,"abstract":"<p><p>We present an implementation of the quantum mechanics/molecular mechanics (QM/MM) method for periodic systems using GPU accelerated QM methods, a distributed multipole formulation of the electrostatics, and a pseudobond treatment of the QM/MM boundary. We demonstrate that our method has well-controlled errors, stable self-consistent QM convergence, and energy-conserving dynamics. We further describe an application to the catalytic kinetics of chorismate mutase. Using an accurate hybrid functional reparametrized to coupled cluster energetics, our QM/MM simulations highlight the sensitivity in the calculated rate to the choice of quantum method, quantum region selection, and local protein conformation. Our work is provided through the open-source PySCF package using acceleration from the GPU4PySCF module.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"803-816"},"PeriodicalIF":5.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Integral-Direct GOSTSHYP Algorithm for the Computation of High Pressure Effects on Molecular and Electronic Structure.","authors":"Ansgar Pausch, Felix Zeller, Tim Neudecker","doi":"10.1021/acs.jctc.4c01502","DOIUrl":"10.1021/acs.jctc.4c01502","url":null,"abstract":"<p><p>To simulate the effects of high pressure on molecular and electronic structure, methods based on the polarizable continuum model have emerged as a serious contender to the conventionally employed periodic boundary conditions. In this work, we present a highly efficient integral-direct algorithm for the Gaussians On Surface Tesserae Simulate HYdrostatic Pressure (GOSTSHYP) method. We examine the efficiency of this implementation on large chains of α-d-glucose units. Furthermore, we investigate the effects of high pressure on the binding energy of a supersystem consisting of a buckminster fullerene and a corannulene pincer system, and juxtapose various types of surfaces that constitute the boundary between the molecule and the implicit solvent. Our efficient implementation of the GOSTSHYP model paves the way for large-scale simulations of molecules under pressure.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"747-761"},"PeriodicalIF":5.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}