检索结果-内蒙古大学图书馆

Ethylene Glycol-Manipulated Syntheses of Calcium Carbonate Particles and dNA Capsules toward Efficient ATP-Responsive Cargo Release

引用

ACS Applied Bio Materials 2023年第8期6卷 3351-3360页

作者： Lin, Yu-Hsuan Singuru, Murali Mohana Rao Marpaung, david Septian Sumanto Liao, Wei-Ching Chuang, Min-Chieh Department of Chemistry Tunghai University Taichung407224 Taiwan International Ph.D. Program in Biomedical and Materials Science Tunghai University Taichung407224 Taiwan Department of Biosystems Engineering Institut Teknologi Sumatera Lampung Selatan35365 Indonesia Institute of Biochemistry and Molecular Biology National Yang Ming Chiao Tung University Taipei112304 Taiwan

Cargo molecule-encapsulated dNA capsules synthesized with a solid sacrificial template have elicited significant interest in the last decade and have been used for active materials in applications ranging from biosensors to drug delivery. However, the correlation between template properties and the subsequent assembly and triggered release behavior of the resultant carriers remain uninvestigated. In this study, ethylene glycol (EG) was added during the CaCO3 precipitation synthesis to yield particles of various sizes and surface properties, and the adenosine triphosphate (ATP)-responsive release characteristics of the fabricated dNA capsules affected by these particle properties were investigated. The geometry, crystallization, and surface morphology of the CaCO3 particles co-precipitated at various EG concentrations were characterized. We discuss the integrity of cross-linking hybridization, fluorescent molecule internalization, degree of leakage, and release efficiency of the resulting dNA capsules and their relevance brought by particle properties. To achieve efficient encapsulation and cargo release, the surface roughness of the CaCO3 particles was explored and was deemed a key determinant of the compactness of the dNA shell after template removal. This effect was particularly strong in CaCO3 particles in connection with high EG concentrations. The dNA capsules fabricated using 83% EG exhibited low leakage, high loading, and moderate release efficiencies as well as a greater apparent association constant with ATP due to their small particle size and the high-integrity dNA shells. © 2023 American Chemical Society.

关键词： Ethylene glycol

来源：评论

学校读者我要写书评

暂无评论

Relative Binding Free Energy Estimation of Congeneric Ligands and Macromolecular Mutants with the Alchemical Transfer with Coordinate Swapping Method

arXiv

引用

arXiv 2024年

作者： Gallicchio, Emilio Department of Chemistry and Biochemistry Brooklyn College The City University of New York New YorkNY11210 United States Ph.D. Program in Chemistry The Graduate Center The City University of New York New YorkNY10016 United States Ph.D. Program in Biochemistry The Graduate Center The City University of New York New YorkNY10016 United States

We present the Alchemical Transfer with Coordinate Swapping (ATS) method to enable the calculation of the relative binding free energies between large congeneric ligands and single-point mutant peptides to protein receptors with the Alchemical Transfer Method (ATM) framework. Similarly to ATM, the new method implements the alchemical transformation as a coordinate transformation, and works with any unmodified force fields and standard chemical topologies. Unlike ATM, which transfers the whole ligands in and out of the receptor binding site, ATS limits the magnitude of the alchemical perturbation by transferring only the portion of the molecules that differ between the the bound and unbound ligands. The common region of the two ligands, which can be arbitrarily large, is unchanged and does not contribute to the magnitude and statistical fluctuations of the perturbation energy. Internally, the coordinates of the atoms of the common regions are swapped to maintain the integrity of the covalent bonding data structures of the molecular dynamics engine. The work successfully validates the method on protein-ligand and protein-peptide RBFE benchmarks. This advance paves the road for the application of the relative binding free energy Alchemical Transfer Method protocol to study the effect of protein and nucleic acid mutations on the binding affinity and specificity of macromolecular complexes. © 2024, CC BY.

关键词： Peptides

来源：评论

学校读者我要写书评

暂无评论

Potential distribution Theory of Alchemical Transfer

arXiv

引用

arXiv 2024年

作者： Azimi, Solmaz Gallicchio, Emilio Ph.D. Program in Biochemistry The Graduate Center of the City University of New York New YorkNY United States Program in Chemistry The Graduate Center of the City University of New York New YorkNY United States

We present an analytical description of the Alchemical Transfer Method (ATM) for molecular binding using the Potential distribution Theory (PdT) formalism. ATM models the binding free energy by mapping the bound and unbound states of the complex by translating the ligand coordinates. PdT relates the free energy and the probability densities of the perturbation energy along the alchemical path to the probability density at the initial state, which is the unbound state of the complex in the case of a binding process. Hence, the ATM probability density of the transfer energy at the unbound state is first related by a convolution operation of the probability densities for coupling the ligand to the solvent and coupling it to the solvated receptor–for which analytical descriptions are available–with parameters obtained from maximum likelihood analysis of data from double-decoupling alchemical calculations. PdT is then used to extend this analytical description along the alchemical transfer pathway. We tested the theory on the alchemical binding of five guests to the TEMOA host from the SAMPL8 benchmark set. In each case, the probability densities of the perturbation energy for transfer along the alchemical transfer pathway obtained from numerical calculations match those predicted from the theory and double-decoupling simulations. The work provides a solid theoretical foundation for alchemical transfer, offers physical insights on the form of the probability densities observed in alchemical transfer calculations, and confirms the conceptual and numerical equivalence between the alchemical transfer and double-decoupling processes. © 2024, CC BY.

关键词： Ligands

来源：评论

学校读者我要写书评

暂无评论

Performance and Analysis of the Alchemical Transfer Method for Binding Free Energy Predictions of diverse Ligands

arXiv

引用

arXiv 2023年

作者： Chen, Lieyang Wu, Yujie Wu, Chuanjie Silveira, Ana Sherman, Woody Xu, Huafeng Gallicchio, Emilio Roivant Sciences 151 W 42nd Street 15th Floor New YorkNY10036 United States Atommap Corporation New YorkNY10017 United States Psivant Therapeutics 451 D Street BostonMA02210 United States Department of Chemistry Brooklyn College of the City University of New York New YorkNY United States Ph.D. Program in Chemistry The Graduate Center of the City University of New York New YorkNY United States Ph.D. Program in Biochemistry The Graduate Center of the City University of New York New YorkNY United States

The Alchemical Transfer Method (ATM) is herein validated against the relative binding free energies of a diverse set of protein-ligand complexes. We employed a streamlined setup workflow, a bespoke force field, and the AToM-OpenMM software to compute the relative binding free energies (RBFE) of the benchmark set prepared by Schindler and collaborators at Merck KGaA. This benchmark set includes examples of standard small R-group ligand modifications as well as more challenging scenarios, such as large R-group changes, scaffold hopping, formal charge changes, and charge-shifting transformations. The novel coordinate perturbation scheme and a dual-topology approach of ATM address some of the challenges of single-topology alchemical relative binding free energy methods. Specifically, ATM eliminates the need for splitting electrostatic and Lennard-Jones interactions, atom mapping, defining ligand regions, and post-corrections for charge-changing perturbations. Thus, ATM is simpler and more broadly applicable than conventional alchemical methods, especially for scaffold-hopping and charge-changing transformations. Here, we performed well over 500 relative binding free energy calculations for eight protein targets and found that ATM achieves accuracy comparable to existing state-of-the-art methods, albeit with larger statistical fluctuations. We discuss insights into specific strengths and weaknesses of the ATM method that will inform future deployments. This study confirms that ATM is applicable as a production tool for relative binding free energy (RBFE) predictions across a wide range of perturbation types within a unified, open-source framework. © 2023, CC BY.

关键词： Ligands

来源：评论

学校读者我要写书评

暂无评论

Environmental Assessment in Fine Jewelry in the U.S.-Mexico's Paso del Norte Region: A Qualitative Study Via X-Ray Fluorescence Spectroscopy

SSRN

引用

SSRN 2022年

作者： Lerma, Maricarmen Banu, Kazi Saima Gardea-Torresdey, Jorge L. Environmental Sciences and Engineering Ph.D. Program The University of Texas at El Paso 500 West University Avenue El PasoTX79968 United States Department of Chemistry and Biochemistry The University of Texas at El Paso 500 West University Avenue El PasoTX79968 United States

Heavy metal contamination in raw materials has spread widely in the United States. The high increased number of recalls in consumer products and the lack of stricter regulations in the raw materials to be used in the jewelry industry have raised concerns among consumers. Studies in low-cost jewelry have shown the presence and high content of heavy metals;this environmental problem led to a child’s death after swallowing a charm containing elevated levels of lead. Exposure to heavy metals, through inhalation, mouth, and skin contact, causes adverse health effects in children and adults. Exposure to lead (Pb) affects mainly the nervous system and brain development, exposure to cadmium (Cd) causes damage to liver, kidneys, and lungs, and potentially lead to cancer, and nickel (Ni) exposure causes severe dermatitis;thus, the importance and impact of studies of this nature cannot be overstated. This qualitative assessment has been performed in fine jewelry, as heavy metal contamination is widespread in the United States. This research also fills a gaping knowledge gap since previous studies were only conducted on low-cost jewelry. In this study, conducted in the Paso del Norte region, one hundred and forty-three pieces of fine jewelry were evaluated for the presence of heavy metals using X-ray fluorescence spectroscopy. Our study showed that 61 samples (42.7%) showed the presence of nickel (Ni) in the metal alloy, prevailing in jewelry pieces with lower percentage of gold (≤10K). Eighteen samples showed the presence of lead (Pb) in gemstones, 11 pieces of these samples (7.7% total) had less than 33.3% gold (10K);however, none of the samples showed the presence of Pb in the metal alloy. Lead found in gemstones may be bioaccessible and pose a potential health hazard to children and adults. © 2022, The Authors. All rights reserved.

关键词： Costs

来源：评论

学校读者我要写书评

暂无评论

Relative binding free energy calculations for ligands with diverse scaffolds with the alchemical transfer method

arXiv

引用

arXiv 2021年

作者： Azimi, Solmaz Khuttan, Sheenam Wu, Joe Z. Pal, Rajat K. Gallicchio, Emilio Department of Chemistry Brooklyn College of the City University of New York New YorkNY United States Ph.D. Program in Biochemistry Graduate Center of the City University of New York New YorkNY United States Ph.D. Program in Chemistry Graduate Center of the City University of New York New YorkNY United States Roivant Sciences BostonMA United States

We present an extension of Alchemical Transfer Method (ATM) for the estimation of relative binding free energies of molecular complexes applicable to conventional as well as scaffold-hopping alchemical transformations. The method, named ATM-RBFE, implemented in the free and open-source OpenMM molecular simulation package, aims to provide a simpler and more generally applicable route to the calculation of relative binding free energies than is currently available. The method is based on sound statistical mechanics theory and a novel coordinate perturbation scheme designed to swap the positions of a pair of ligands such that one is transferred from the bulk solvent to the receptor binding site while the other moves simultaneously in the opposite direction. The calculation is conducted directly using a single solvent box prepared using conventional setup tools, without splitting of electrostatic and non-electrostatic transformations, and without pairwise soft-core potentials. ATM-RBFE is validated here against the absolute binding free energies of the SAMPL8 GdCC host-guest benchmark set and against a benchmark set of estrogen receptor α complexes. In each case the method yields self-consistent and converged relative binding free energy estimates in agreement with absolute binding free energies, reference literature values as well as experimental measurements. © 2021, CC BY.

关键词： Binding energy

来源：评论

学校读者我要写书评

暂无评论

Alchemical transfer approach to absolute binding free energy estimation

arXiv

引用

arXiv 2021年

作者： Wu, Joe Z. Azimi, Solmaz Khuttan, Sheenam deng, Nanjie Gallicchio, Emilio Department of Chemistry Brooklyn College of the City University of New York New YorkNY United States Ph.D. Program in Chemistry The Graduate Center of the City University of New York New YorkNY United States Ph.D. Program in Biochemistry The Graduate Center of the City University of New York New YorkNY United States Department of Chemistry and Physical Sciences Pace University New YorkNY10038 United States

The Alchemical Transfer Method (ATM) for the calculation of standard binding free energies of non-covalent molecular complexes is presented. The method is based on a coordinate displacement perturbation of the ligand between the receptor binding site and the explicit solvent bulk, and a thermodynamic cycle connected by a symmetric intermediate in which the ligand interacts with the receptor and solvent environments with equal strength. While the approach is alchemical, the implementation of ATM is as straightforward as for physical pathway methods of binding. The method is applicable in principle with any force field, it does not require splitting the alchemical transformations into electrostatic and non-electrostatic steps, and it does not require soft-core pair potentials. We have implemented ATM as a freely available and open-source plugin of the OpenMM molecular dynamics library. The method and its implementation are validated on the SAMPL6 SAMPLing host-guest benchmark set. The work paves the way to streamlined alchemical relative and absolute binding free energy implementations on many molecular simulation packages and with arbitrary energy functions including polarizable, quantum-mechanical, and artificial neural network potentials. © 2021, CC BY.

关键词： Electrostatics

来源：评论

学校读者我要写书评

暂无评论

Integrating Computation, Experiment, and Machine Learning in the design of Peptide-Based Supramolecular Materials and Systems

引用

Angewandte Chemie 2023年第18期135卷

作者： Maithreyi Ramakrishnan Alexander van Teijlingen Tell Tuttle R. V. Ulijn Advanced Science Research Center (ASRC) at the Graduate Center City University of New York (CUNY) New York NY 10031 USA Department of Chemistry Hunter College The City University of New York New York NY 10065 USA Ph.D. Program in Chemistry The Graduate Center of the City University of New York New York NY 10016 USA Pure and Applied Chemistry University of Strathclyde 295 Cathedral Street Glasgow G1 1XL UK Ph.D. Program in Chemistry and PhD program in Biochemistry The Graduate Center of the City University of New York New York NY 10016 USA

Interest in peptide-based supramolecular materials has grown extensively since the 1980s and the application of computational methods has paralleled this. These methods contribute to the understanding of experimental observations based on interactions and inform the design of new supramolecular systems. They are also used to virtually screen and navigate these very large design spaces. Increasingly, the use of artificial intelligence is employed to screen far more candidates than traditional methods. Based on a brief history of computational and experimentally integrated investigations of peptide structures, we explore recent impactful examples of computationally driven investigation into peptide self-assembly, focusing on recent advances in methodology development. It is clear that the integration between experiment and computation to understand and design new systems is becoming near seamless in this growing field.

关键词： Computation Molecular dynamics Peptides Self-Assembly Supramolecular chemistry

来源：评论

学校读者我要写书评

暂无评论

dual-Targeting EGCG/NO-Supplying protein assembled nanoparticles with Multi-Synergistic effects against atherosclerosis

引用

Chemical Engineering Journal 2024年 493卷

作者： Lin, Chi Cheng, Tsai-Mu Liu, Yun-Chun Hsu, Fang-Yu Shih, Chun-Ming Tsai, Min-Lang Shih, Chun-Che Mi, Fwu-Long Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei11031 Taiwan The PhD Program for Translational Medicine College of Medical Science and Technology Taipei Medical University Taipei11031 Taiwan Taipei Heart Institute Taipei Medical University Taipei11031 Taiwan Department of Food Science National Taiwan Ocean University Keelung20224 Taiwan Department of Biochemistry and Molecular Cell Biology School of Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Division of Cardiology and Cardiovascular Research Center Taipei Medical University Hospital Taipei11031 Taiwan Division of Cardiovascular Surgery Department of Surgery Wan Fang Hospital Taipei Medical University Taipei11031 Taiwan Institute of Clinical Medicine School of Medicine National Yang-Ming Chiao Tung University Taipei Taiwan Department of Surgery School of Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Graduate Institute of Nanomedicine and Medical Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan International Ph.D. Program for Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei Taiwan

Limited therapeutic options are available to effectively preventing atherosclerosis. Inflammatory endothelial cells, foamy macrophages, and high protease levels contribute to atherosclerotic plaque formation. Studies have shown that catechins effectively scavenge reactive oxygen species (ROS), inhibit monocyte adhesion and reduce cholesterol levels, while nitric oxide (NO) enhances endothelial function. However, due to the poor stability and bioavailability of catechins and the toxicity from the burst release of current synthetic small molecules NO donor, effective delivery of these bioactive compounds to treat atherosclerosis is still a challenge. Herein, a catechin/protein-based NO donor co-delivery nanosystem was designed for combinatorial anti-atherosclerotic therapy. We engineered a (−)-epigallocatechin-3-gallate (EGCG)/NO-releasing protein co-assembled nanocomplex based on specific catechin-protein interactions. Furthermore, the nanocomplex was surface modified with fucoidan (Fu), a sulfated polysaccharide with anti-inflammatory activity. This nanocomplex exhibits sensitivity to ROS, ph, and enzymes. The Fu-functionalized nanoparticles specifically accumulates in atherosclerotic plaques mediated by P-selectin on inflamed endothelial cells and scavenger receptor A (SR-A) on foamy macrophages. Under environmental stimuli that simulate the condition of plaque, the nanoparticles are readily activated to release EGCG and NO in response to excess ROS and high protease levels, exerting the multi-synergistic anti-atherosclerosic effects on reducing monocyte adhesion, promoting NO production to proliferate endothelial cells, lowering ROS levels, and decreasing the foam cell formation in vitro, and reducing lipid accumulation, plaque size, and inflammatory cytokines release in high-fat diet-induced atherosclerosis model in ApoE−/− mice. The integration of plaques targeting ability and multiple therapeutic functions can provide an advanced therapeutic strategy for athero

关键词： Nitric oxide

来源：评论

学校读者我要写书评

暂无评论

OpenMM 8: Molecular dynamics Simulation with Machine Learning Potentials

arXiv

引用

arXiv 2023年

作者： Eastman, Peter Galvelis, Raimondas Peláez, Raúl P. Abreu, Charlles R.A. Farr, Stephen E. Gallicchio, Emilio Gorenko, Anton Henry, Michael M. Hu, Frank Huang, Jing Krämer, Andreas Michel, Julien Mitchell, Joshua A. Pande, Vijay S. Rodrigues, João P.G.L.M. Rodriguez-Guerra, Jaime Simmonett, Andrew C. Singh, Sukrit Swails, Jason Turner, philip Wang, Yuanqing Zhang, Ivy Chodera, John d. de Fabritiis, Gianni Markland, Thomas E. Department of Chemistry Stanford University StanfordCA94305 United States Acellera Labs C Dr Trueta 183 Barcelona08005 Spain C Dr. Aiguader 88 Barcelona08003 Spain Chemical Engineering Department School of Chemistry Federal University of Rio de Janeiro Rio de Janeiro68542 Brazil Redesign Science Inc. 180 Varick St. New YorkNY10014 United States EaStCHEM School of Chemistry University of Edinburgh EH9 3FJ United Kingdom Department of Chemistry and Biochemistry Brooklyn College The City University of New York NY United States Ph.D. Program in Chemistry Ph.D. Program in Biochemistry The Graduate Center of the City University of New York New YorkNY United States Stream HPC Koningin Wilhelminaplein 1 - 40601 Amsterdam1062 HG Netherlands Computational and Systems Biology Program Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New YorkNY10065 United States Key Laboratory of Structural Biology of Zhejiang Province School of Life Sciences Westlake University 18 Shilongshan Road Zhejiang Hangzhou310024 China Department of Mathematics and Computer Science Freie Universität Berlin Arnimallee 12 Berlin14195 Germany The Open Force Field Initiative Open Molecular Software Foundation DavisCA95616 United States Andreessen Horowitz 2865 Sand Hill Rd Menlo ParkCA94025 United States Department of Structural Biology Stanford University StanfordCA94305 United States Charité Universitätsmedizin Berlin In silico Toxicology and Structural Bioinformatics Virchowweg 6 Berlin10117 Germany Laboratory of Computational Biology National Heart Lung and Blood Institute National Institutes of Health BethesdaMD20892 United States Entos Inc. 9310 Athena Circle La Jolla CA92037 United States College of Engineering Virginia Polytechnic Institute State University BlacksburgVA24061 United States Simons Center for Computational Physical Chemistry Center for Data Science New York University 24 Waverly Place New YorkNY10004 United States T

Machine learning plays an important and growing role in molecular simulation. The newest version of the OpenMM molecular dynamics toolkit introduces new features to support the use of machine learning potentials. Arbitrary PyTorch models can be added to a simulation and used to compute forces and energy. A higher-level interface allows users to easily model their molecules of interest with general purpose, pretrained potential functions. A collection of optimized CUdA kernels and custom PyTorch operations greatly improves the speed of simulations. We demonstrate these features on simulations of cyclin-dependent kinase 8 (CdK8) and the green fluorescent protein (GFP) chromophore in water. Taken together, these features make it practical to use machine learning to improve the accuracy of simulations at only a modest increase in cost. Copyright © 2023, The Authors. All rights reserved.

关键词： Machine learning

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：