ACS Publications最新文献

{"title":"Descriptor-Free Collective Variables from Geometric Graph Neural Networks.","authors":"Jintu Zhang, Luigi Bonati, Enrico Trizio, Odin Zhang, Yu Kang, TingJun Hou, Michele Parrinello","doi":"10.1021/acs.jctc.4c01197","DOIUrl":"10.1021/acs.jctc.4c01197","url":null,"abstract":"<p><p>Enhanced sampling simulations make the computational study of rare events feasible. A large family of such methods crucially depends on the definition of some collective variables (CVs) that could provide a low-dimensional representation of the relevant physics of the process. Recently, many methods have been proposed to semiautomatize the CV design by using machine learning tools to learn the variables directly from the simulation data. However, most methods are based on feedforward neural networks and require some user-defined physical descriptors. Here, we propose bypassing this step using a graph neural network to directly use the atomic coordinates as input for the CV model. This way, we achieve a fully automatic approach to CV determination that provides variables invariant under the relevant symmetries, especially the permutational one. Furthermore, we provide different analysis tools to favor the physical interpretation of the final CV. We prove the robustness of our approach using different methods from the literature for the optimization of the CV, and we prove its efficacy on several systems, including a small peptide, an ion dissociation in explicit solvent, and a simple chemical reaction.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"10787-10797"},"PeriodicalIF":5.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811463","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":"Faster Sampling in Molecular Dynamics Simulations with TIP3P-F Water.","authors":"José Guadalupe Rosas Jiménez, Balázs Fábián, Gerhard Hummer","doi":"10.1021/acs.jctc.4c00990","DOIUrl":"10.1021/acs.jctc.4c00990","url":null,"abstract":"<p><p>The need for short time steps currently limits routine atomistic molecular dynamics (MD) simulations to the microsecond time scale. For long time steps, the numerical integration of the equations of motion becomes unstable, resulting in catastrophic crashes. Here, we combine mass repartitioning and rescaling to construct a water model that increases the sampling efficiency in biomolecular simulations without compromising integration stability and with preserved structural and thermodynamic properties. The resulting \"fast water\" is then used with a time step as before in combination with standard force fields. The reduced water viscosity and faster diffusion result in proportionally faster sampling of the larger-scale motions in the conformation space of both solute and solvent. We illustrate this approach by developing TIP3P-F based on the popular TIP3P model of water. A roughly 2-fold boost in the sampling efficiency at minimal cost in accuracy is substantial and helps lower the energy impact of large-scale MD simulations. The approach is general and can readily be applied to other water models and different types of solvents.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"11068-11081"},"PeriodicalIF":5.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816709","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":"Convergent Concordant Mode Approach for Molecular Vibrations: CMA-2.","authors":"Nathaniel L Kitzmiller, Mitchell E Lahm, Laura N Olive Dornshuld, Jincan Jin, Wesley D Allen, Henry F Schaefer Iii","doi":"10.1021/acs.jctc.4c01240","DOIUrl":"10.1021/acs.jctc.4c01240","url":null,"abstract":"<p><p>The concordant mode approach (CMA) is a promising new scheme for dramatically increasing the system size and level of theory achievable in quantum chemical computations of molecular vibrational frequencies. Here, we achieve advances in the CMA hierarchy by computations targeting CCSD(T)/cc-pVTZ (coupled cluster singles and doubles with perturbative triples using a correlation-consistent polarized-valence triple-ζ basis set) benchmarks within the G2 molecular test set, executing a statistical analysis for 1501 frequencies from 111 compounds and then separately solving the refractory case of pyridine. First, MP2/cc-pVTZ (second-order Møller-Plesset perturbation theory with the same basis set) proves to be an excellent and preferred choice for generating the underlying (Level B) normal modes of the CMA scheme. Utilizing this Level B within the CMA-0A method reproduces the 1501 benchmark frequencies with a mean absolute error (MAE) of only 0.11 cm^-1 and an attendant standard deviation of 0.49 cm^-1. Second, a convergent CMA-2 method is constituted that allows efficient computation of higher level (Level A) frequencies to any reasonable accuracy threshold by using only Hartree-Fock (HF) and MP2 or density functional theory (DFT) data to generate ξ parameters, which select the sparse off-diagonal force field elements for explicit evaluation at Level A. When Level B = MP2/cc-pVTZ, a cutoff of ξ = 0.02 provides an average maximum absolute error per molecule of only 0.17 cm^-1 by incurring merely a 33% increase in average cost over CMA-0A. This CMA-2 method also eradicates the 4 problematic CMA-0A outliers of pyridine with even less effort (ξ = 0.04, 22% increase). Finally, the newly developed CMA procedures are shown to be highly successful when applied to 1-(1<i>H</i>-pyrrol-3-yl)ethanol, a new test molecule with diverse types of vibration.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"10886-10898"},"PeriodicalIF":5.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821530","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":"Advances in Aerosol Nanostructuring: Functions and Control of Next-Generation Particles.","authors":"Eka Lutfi Septiani, Takashi Ogi","doi":"10.1021/acs.langmuir.4c02867","DOIUrl":"10.1021/acs.langmuir.4c02867","url":null,"abstract":"<p><p>Nanostructured particles (NSPs), with their remarkable properties at the nanoscale, possess key functions required for unlocking a sustainable future. Fabricating these particles using aerosol methods and spraying processes enables precise control over the particle morphology, structure, composition, and crystallinity during in-flight transformation. In this Perspective, the significant impact of NSPs on technological advancement for energy and environmental applications is discussed. Furthermore, incorporating in situ/operando assessment techniques alongside machine and deep learning is explored. Finally, the future development trends and the perspective on the advancing NSPs synthesis via aerosol process are elaborated for further driving innovations for supersmart and carbon-neutral society.</p>","PeriodicalId":50,"journal":{"name":"Langmuir","volume":" ","pages":"26789-26799"},"PeriodicalIF":3.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638105","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":"Assessing Exchange-Correlation Functionals for Accurate Densities of Solids.","authors":"Ayoub Aouina, Pedro Borlido, Miguel A L Marques, Silvana Botti","doi":"10.1021/acs.jctc.4c01042","DOIUrl":"10.1021/acs.jctc.4c01042","url":null,"abstract":"<p><p>The success of Kohn-Sham density functional theory in predicting electronic properties from first-principles is key to its ubiquitous presence in condensed matter research. Central to this theory is the exchange-correlation functional, which can only be written in an approximate form using a handful of exact constraints. A recent criticism of these approximations is that they are designed to give an accurate description of the energy at the expense of a poor representation of the density, which is contrary to the spirit of density functional theory. These conclusions are drawn from studies of atoms or small molecules, where exact results are available. To shed light on this issue, we use the almost exact densities and energies of three prototypical solids (a semiconductor, silicon, an insulator, sodium chloride, and a metal, copper) to compare the performance of exchange-correlation functionals from all rungs of Jacob's ladder. By examining their errors in reproducing both energy and density, we show that several hybrids and semilocal functionals perform consistently well. Furthermore, functionals built to reproduce exact constraints tend to be among the top performers for all tested material classes, strengthening the argument for using these constraints in functional construction. On average, functionals published up to the early 2000s simultaneously improve the prediction of both densities and energies. This is often not the case for more recent functionals, although errors in energy and density continue to evolve in a correlated manner.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"10852-10860"},"PeriodicalIF":5.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764706","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":"Dynamic Correlation Analysis between Stress-Strain Curve and Polymer Film Structure Using Persistent Homology.","authors":"Ryuhei Sato, Shinya Kawakami, Hirotaka Ejima, Takahiro Ujii, Koichi Sato, Takanori Ichiki, Yasushi Shibuta","doi":"10.1021/acs.jctc.4c01418","DOIUrl":"10.1021/acs.jctc.4c01418","url":null,"abstract":"<p><p>Coarse-grained molecular dynamics (CG-MD) simulations and subsequent persistent homology (PH) analysis were performed to correlate the structure and stress-strain behavior of polymer films. During uniaxial tensile MD simulations, the first principal component of the persistence diagram obtained by principal component analysis (PCA) was in good agreement with the stress-strain curve. This indicates that PH + PCA can identify critical ring structures relevant to the dynamic changes in MD simulations without requiring any prior knowledge. Inverse analysis of the persistence diagram revealed that smaller rings with ten or fewer CG beads mainly contribute to changes in the first principal component of the persistence diagram. This is due to the properties of the poly(ethylene oxide) chain, which favors the formation of a seven-membered helical structure during the self-entanglement process. The PH + PCA approach successfully reproduced the stress-strain curves for polymers with different nonbonding interactions and bond lengths. Moreover, the changes in the yield stress of each polymer film were qualitatively explained by the ring distribution in the persistence diagram. These results suggest that persistent homology analysis followed by PCA provides a versatile and powerful framework for correlating structural features with physical properties, such as ring distribution and stress-strain behavior in polymer films.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"10798-10806"},"PeriodicalIF":5.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764715","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":"Modeling Ligand Binding Site Water Networks with Site Identification by Ligand Competitive Saturation: Impact on Ligand Binding Orientations and Relative Binding Affinities.","authors":"Anmol Kumar, Himanshu Goel, Wenbo Yu, Mingtian Zhao, Alexander D MacKerell","doi":"10.1021/acs.jctc.4c01165","DOIUrl":"10.1021/acs.jctc.4c01165","url":null,"abstract":"<p><p>Appropriate treatment of water contributions to protein-ligand interactions is a very challenging problem in the context of adequately determining the number of waters to investigate and undertaking conformational sampling of the ligands, the waters, and the surrounding protein. In the present study, an extension of the Site Identification by Ligand Competitive Saturation-Monte Carlo (SILCS-MC) docking approach is presented that enables the determination of the location of water molecules in the binding pocket and their impact on the predicted ligand binding orientation and affinities. The approach, termed SILCS-WATER, involves MC sampling of the ligand along with explicit water molecules in a binding site followed by selection of a subset of waters within specified energetic and distance cutoffs that contribute to ligand binding and orientation. To allow for convergence of both the water and ligand orientations, SILCS-WATER is based on just the overlap of the ligand and water with the SILCS FragMaps and the interaction energy between the waters and ligand. Results show that the SILCS-WATER methodology can capture important waters and improve ligand binding orientations. For 6 of 10 multiple ligand-protein systems, the method improved relative binding affinity prediction against experimental results, with substantial improvements in five systems, when compared to standard SILCS-MC. Improved reproduction of crystallographic ligand binding orientations is shown to be an indicator of when SILCS-WATER will yield improved binding affinity correlations. The method also identifies waters interacting with ligands that occupy unfavorable locations with respect to the protein whose displacement through the appropriate ligand modifications should improve ligand binding affinity. Results are consistent with the binding affinity being modeled as a ligand-water complex interacting with the protein. The presented approach offers new possibilities in revealing water networks and their contributions to the binding orientation and affinity of a ligand for a protein and is anticipated to be of utility for computer-aided drug design.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"11032-11048"},"PeriodicalIF":5.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783343","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":"Quantum Electrodynamics in High-Harmonic Generation: Multitrajectory Ehrenfest and Exact Quantum Analysis.","authors":"Sebastián de-la-Peña, Ofer Neufeld, Matan Even Tzur, Oren Cohen, Heiko Appel, Angel Rubio","doi":"10.1021/acs.jctc.4c01206","DOIUrl":"https://doi.org/10.1021/acs.jctc.4c01206","url":null,"abstract":"<p><p>High-harmonic generation (HHG) is a nonlinear process in which a material sample is irradiated by intense laser pulses, causing the emission of high harmonics of incident light. HHG has historically been explained by theories employing a classical electromagnetic field, successfully capturing its spectral and temporal characteristics. However, recent research indicates that quantum-optical effects naturally exist or can be artificially induced in HHG, such as entanglement between emitted harmonics. Even though the fundamental equations of motion for quantum electrodynamics (QED) are well-known, a unifying framework for solving them to explore HHG is missing. So far, numerical solutions have employed a wide range of basis-sets, methods, and untested approximations. Based on methods originally developed for cavity polaritonics, here we formulate a numerically accurate QED model consisting of a single active electron and a single quantized photon mode. Our framework can, in principle, be extended to higher electronic dimensions and multiple photon modes to be employed in <i>ab initio</i> codes for realistic physical systems. We employ it as a model of an atom interacting with a photon mode and predict a characteristic minimum structure in the HHG yield vs phase-squeezing. We find that this phenomenon, which can be used for novel ultrafast quantum spectroscopies, is partially captured by a multitrajectory Ehrenfest dynamics approach, with the exact minima position sensitive to the level of theory. On the one hand, this motivates using multitrajectory approaches as an alternative for costly exact calculations. On the other hand, it suggests an inherent limitation of the multitrajectory formalism, indicating the presence of entanglement and true quantum effects (especially prominent for atomic and molecular resonances). Our work creates a roadmap for a universal formalism of QED-HHG that can be employed for benchmarking approximate theories, predicting novel phenomena for advancing quantum applications, and for the measurements of entanglement and entropy.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880707","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":"Tudor-Containing Methyl-Lysine and Methyl-Arginine Reader Proteins: Disease Implications and Chemical Tool Development.","authors":"Mélanie Uguen, Tongkun Liu, Lindsey I James, Stephen V Frye","doi":"10.1021/acschembio.4c00661","DOIUrl":"https://doi.org/10.1021/acschembio.4c00661","url":null,"abstract":"<p><p>Tudor domains are histone readers that can recognize various methylation marks on lysine and arginine. This recognition event plays a key role in the recruitment of other epigenetic effectors and the control of gene accessibility. The Tudor-containing protein family contains 42 members, many of which are involved in the development and progression of various diseases, especially cancer. The development of chemical tools for this family will not only lead to a deeper understanding of the biological functions of Tudor domains but also lay the foundation for therapeutic discoveries. In this review, we discuss the role of several Tudor domain-containing proteins in a range of relevant diseases and progress toward the development of chemical tools such as peptides, peptidomimetics, or small-molecules that bind Tudor domains. Overall, we highlight how Tudor domains are promising targets for therapeutic development and would benefit from the development of novel chemical tools.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delivery of Monomethyl Auristatin F to the Tumor Microenvironment with Noninternalizing Fibroblast Activation Protein-Cleavable Small Molecule-Drug Conjugates Elicits Potent <i>In Vivo</i> Anticancer Activity.","authors":"Matilde Bocci, Lucrezia Principi, Ettore Gilardoni, Dario Neri, Samuele Cazzamalli, Andrea Galbiati","doi":"10.1021/acs.bioconjchem.4c00503","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00503","url":null,"abstract":"<p><p>OncoFAP is an ultrahigh affinity ligand of fibroblast activation protein (FAP), a tumor-associated antigen overexpressed in the stroma of the majority of solid tumors. OncoFAP has been previously implemented as a tumor-homing moiety for the development of small molecule drug conjugates (SMDCs). In the same context, the glycine--proline dipeptide was included with the aim to selectively undergo cleavage only in the presence of the target FAP, triggering the consequent release of the cytotoxic payload in the tumor microenvironment. In this work, we evaluate the use of monomethyl auristatin F (MMAF) as a payload, a close derivative of MMAE bearing a charged carboxylic acid that hampers its cellular permeability, typically employed in the development of internalizing antibody-drug conjugates. The novel OncoFAP-GlyPro-MMAF and the previously described OncoFAP-GlyPro-MMAE were compared in a head-to-head therapeutic experiment in mice bearing FAP-positive tumors. Surprisingly, the MMAF conjugate mediated potent antitumor activity, despite its poor cellular permeability.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880634","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}