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Random close packing in protein cores

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Physical Review E 2016年第3期93卷 032415-032415页

作者： Jennifer C. Gaines W. Wendell Smith Lynne Regan Corey S. O'Hern Program in Computational Biology and Bioinformatics Yale University New Haven Connecticut 06520 USA Integrated Graduate Program in Physical and Engineering Biology (IGPPEB) Yale University New Haven Connecticut 06520 USA Department of Physics Yale University New Haven Connecticut 06520 USA Department of Molecular Biophysics & Biochemistry Yale University New Haven Connecticut 06520 USA Department of Chemistry Yale University New Haven Connecticut 06520 USA Department of Mechanical Engineering & Materials Science Yale University New Haven Connecticut 06520 USA Department of Applied Physics Yale University New Haven Connecticut 06520 USA

Shortly after the determination of the first protein x-ray crystal structures, researchers analyzed their cores and reported packing fractions ϕ≈0.75, a value that is similar to close packing of equal-sized spheres. A limitation of these analyses was the use of extended atom models, rather than the more physically accurate explicit hydrogen model. The validity of the explicit hydrogen model was proved in our previous studies by its ability to predict the side chain dihedral angle distributions observed in proteins. In contrast, the extended atom model is not able to recapitulate the side chain dihedral angle distributions, and gives rise to large atomic clashes at side chain dihedral angle combinations that are highly probable in protein crystal structures. Here, we employ the explicit hydrogen model to calculate the packing fraction of the cores of over 200 high-resolution protein structures. We find that these protein cores have ϕ≈0.56, which is similar to results obtained from simulations of random packings of individual amino acids. This result provides a deeper understanding of the physical basis of protein structure that will enable predictions of the effects of amino acid mutations to protein cores and interfaces of known structure.

关键词： Protein structure Proteins

Identifying the minimal sets of distance restraints for FRET-assisted protein structural modeling

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arXiv 2024年

作者： Liu, Zhuoyi Grigas, Alex T. Sumner, Jacob Knab, Edward Davis, Caitlin M. O’Hern, Corey S. Department of Mechanical Engineering and Materials Science Yale University New HavenCT06520 United States Integrated Graduate Program in Physical and Engineering Biology Yale University New HavenCT06520 United States Graduate Program in Computational Biology and Bioinformatics Yale University New HavenCT06520 United States Department of Chemistry Yale University New HavenCT06520 United States Department of Physics Yale University New HavenCT06520 United States Department of Applied Physics Yale University New HavenCT06520 United States

Proteins naturally occur in crowded cellular environments and interact with other proteins, nucleic acids, and organelles. Since most previous experimental protein structure determination techniques require that proteins occur in idealized, non-physiological environments, the effects of realistic cellular environments on protein structure are largely unexplored. Recently, Förster resonance energy transfer (FRET) has been shown to be an effective experimental method for investigating protein structure in vivo. Inter-residue distances measured in vivo can be incorporated as restraints in molecular dynamics (MD) simulations to model protein structural dynamics in vivo. Since most FRET studies only obtain inter-residue separations for a small number of amino acid pairs, it is important to determine the minimum number of restraints in the MD simulations that are required to achieve a given root-mean-square deviation (RMSD) from the experimental structural ensemble. Further, what is the optimal method for selecting these inter-residue restraints? Here, we implement several methods for selecting the most important FRET pairs and determine the number of pairs Nr that are needed to induce conformational changes in proteins between two experimentally determined structures. We find that enforcing only a small fraction of restraints, Nr/N 0.08, where N is the number of amino acids, can induce the conformational changes. These results establish the efficacy of FRET-assisted MD simulations for atomic scale structural modeling of proteins in vivo. © 2024, CC BY.

关键词： Conformations

Structural insights into the role of N-terminal integrity in PhoSL for core-fucosylated N-glycan recognition

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International Journal of Biological Macromolecules 2024年 255卷 128309页

作者： Lou, Yuan-Chao Tu, Cheng-Fen Chou, Chun-Chi Yeh, Hsin-Hong Chien, Chia-Yu Sadotra, Sushant Chen, Chinpan Yang, Ruey-Bing Hsu, Chun-Hua Institute of Biomedical Sciences Academia Sinica Taipei115 Taiwan Department of Agricultural Chemistry National Taiwan University Taipei106 Taiwan Chemical Biology and Molecular Biophysics Taiwan International Graduate Program Academia Sinica Taipei115 Taiwan Institute of Bioinformatics and Structural Biology National Tsing Hua University Hsinchu300 Taiwan Biomedical Translation Research Center Academia Sinica Taipei115 Taiwan Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University Taipei110 Taiwan Genome and Systems Biology Degree Program National Taiwan University and Academia Sinica Taipei106 Taiwan Institute of Biochemical Sciences National Taiwan University Taipei106 Taiwan Center for Computational and Systems Biology National Taiwan University Taipei106 Taiwan

PhoSL (Pholiota squarrosa Lectin) has an exceptional binding affinity for biomolecules with core-fucosylated N-glycans. This modification involves the addition of fucose to the inner N-acetylglucosamine within the N-glycan structure and is known to influence many physiological processes. Nevertheless, the molecular interactions underlying high-affinity binding of native PhoSL to core-fucosylated N-glycans remain largely unknown. In this study, we devised a strategy to produce PhoSL with the essential structural characteristics of the native protein (n-PhoSL). To do so, a fusion protein was expressed in E. coli and purified. Then, enzymatic cleavage and incubation with glutathione were utilized to recapitulate the native primary structure and disulfide bonding pattern. Subsequently, we identified the residues crucial for n-PhoSL binding to core-fucosylated chitobiose (N2F) via NMR spectroscopy. Additionally, crystal structures were solved for both apo n-PhoSL and its N2F complex. These analyses suggested a pivotal role of the N-terminal amine in maintaining the integrity of the binding pocket and actively contributing to core-fucose recognition. In support of this idea, the inclusion of additional residues at the N-terminus considerably reduced binding affinity and PhoSL cytotoxicity toward breast cancer cells. Taken together, these findings can facilitate the utilization of PhoSL in basic research, diagnostics and therapeutic strategies. © 2023 Elsevier B.V.

关键词： Proteins

Hypostatic jammed packings of frictionless nonspherical particles

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Physical Review E 2018年第1期97卷 012909-012909页

作者： Kyle VanderWerf Weiwei Jin Mark D. Shattuck Corey S. O'Hern Department of Physics Yale University New Haven Connecticut 06520 USA Department of Mechanics and Engineering Science Peking University Beijing 100871 China Department of Mechanical Engineering & Materials Science Yale University New Haven Connecticut 06520 USA Benjamin Levich Institute and Physics Department The City College of New York New York New York 10031 USA Department of Applied Physics Yale University New Haven Connecticut 06520 USA Graduate Program in Computational Biology and Bioinformatics Yale University New Haven Connecticut 06520 USA

We perform computational studies of static packings of a variety of nonspherical particles including circulo-lines, circulo-polygons, ellipses, asymmetric dimers, dumbbells, and others to determine which shapes form packings with fewer contacts than degrees of freedom (hypostatic packings) and which have equal numbers of contacts and degrees of freedom (isostatic packings), and to understand why hypostatic packings of nonspherical particles can be mechanically stable despite having fewer contacts than that predicted from naive constraint counting. To generate highly accurate force- and torque-balanced packings of circulo-lines and cir-polygons, we developed an interparticle potential that gives continuous forces and torques as a function of the particle coordinates. We show that the packing fraction and coordination number at jamming onset obey a masterlike form for all of the nonspherical particle packings we studied when plotted versus the particle asphericity A, which is proportional to the ratio of the squared perimeter to the area of the particle. Further, the eigenvalue spectra of the dynamical matrix for packings of different particle shapes collapse when plotted at the same A. For hypostatic packings of nonspherical particles, we verify that the number of “quartic” modes along which the potential energy increases as the fourth power of the perturbation amplitude matches the number of missing contacts relative to the isostatic value. We show that the fourth derivatives of the total potential energy in the directions of the quartic modes remain nonzero as the pressure of the packings is decreased to zero. In addition, we calculate the principal curvatures of the inequality constraints for each contact in circulo-line packings and identify specific types of contacts with inequality constraints that possess convex curvature. These contacts can constrain multiple degrees of freedom and allow hypostatic packings of nonspherical particles to be mechanically stable.

关键词： Granular materials Granular packing Jamming

The connection between polymer collapse and the onset of jamming

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arXiv 2023年

作者： Grigas, Alex T. Fisher, Aliza Shattuck, Mark D. O’Hern, Corey S. Graduate Program in Computational Biology and Bioinformatics Yale University New HavenCT06520 United States Integrated Graduate Program in Physical and Engineering Biology Yale University New HavenCT06520 United States Department of Mechanical Engineering and Materials Science Yale University New HavenCT06520 United States Benjamin Levich Institute and Physics Department The City College of New York New YorkNY10031 United States Department of Physics Yale University New HavenCT06520 United States Department of Applied Physics Yale University New HavenCT06520 United States

Previous studies have shown that the interiors of proteins are densely packed, reaching packing fractions that are as large as those found for static packings of individual amino-acid-shaped particles. How can the interiors of proteins take on such high packing fractions given that amino acids are connected by peptide bonds and many amino acids are hydrophobic with attractive interactions? We investigate this question by comparing the structural and mechanical properties of collapsed attractive disk-shaped bead-spring polymers to those of three reference systems: static packings of repulsive disks, of attractive disks, and of repulsive disk-shaped bead-spring polymers. We show that attractive systems quenched to temperatures below the glass transition T Tg and static packings of both repulsive disks and bead-spring polymers possess similar interior packing fractions. Previous studies have shown that static packings of repulsive disks are isostatic at jamming onset, i.e. the number of contacts Nc matches the number of degrees of freedom, which strongly influences their mechanical properties. We find that repulsive polymers are hypostatic at jamming onset, but effectively isostatic when including quartic modes. While attractive disk and polymer packings are hyperstatic, we identify a definition for interparticle contacts for which they can also be considered as effectively isostatic. As a result, we show that the mechanical properties (e.g. scaling of the potential energy with excess contact number and low-frequency contribution to the density of vibrational modes) of weakly attractive disk and polymer packings are similar to those of isostatic repulsive disk and polymer packings. Our results demonstrate that static packings generated via attractive collapse or compression of repulsive particles possess similar structural and mechanical properties. © 2023, CC BY.

关键词： Amino acids

Protein folding as a jamming transition

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arXiv 2024年

作者： Grigas, Alex T. Liu, Zhuoyi Logan, Jack A. Shattuck, Mark D. O’Hern, Corey S. Graduate Program in Computational Biology and Bioinformatics Yale University New HavenCT06520 United States Integrated Graduate Program in Physical and Engineering Biology Yale University New HavenCT06520 United States Department of Mechanical Engineering and Materials Science Yale University New HavenCT06520 United States Benjamin Levich Institute and Physics Department The City College of New York New YorkNY10031 United States Department of Physics Yale University New HavenCT06520 United States Department of Applied Physics Yale University New HavenCT06520 United States

Proteins fold to a specific functional conformation with a densely packed hydrophobic core that controls their stability. We develop a geometric, yet all-atom model for proteins that explains the universal core packing fraction of φc = 0.55 found in experimental measurements. We show that as the hydrophobic interactions increase relative to the temperature, a novel jamming transition occurs when the core packing fraction exceeds φc. The model also recapitulates the global structure of proteins since it can accurately refold to native-like structures from partially unfolded states. © 2024, CC BY.

关键词： Proteins

Theoretical Insights into Co2 Electroreduction on Single and Dual Heteroatom-Doped Diamonds

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SSRN

SSRN 2023年

作者： Injongkol, Yuwanda Zhang, Rui-Qin Montoya, Alejandro Rungrotmongkol, Thanyada Jungsuttiwong, Siriporn Center of Excellence in Biocatalyst and Sustainable Biotechnology Department of Biochemistry Faculty of Science Chulalongkorn University Bangkok10330 Thailand City University of Hong Kong Hong Kong School of Chemical and Biomolecular Engineering The University of Sydney SydneyNSW2006 Australia Program in Bioinformatics and Computational Biology Graduate School Chulalongkorn University Bangkok10330 Thailand Department of Chemistry Faculty of Science Ubon Ratchathani University Ubon Ratchathani34190 Thailand

We employed Periodic Density Functional Theory (DFT) to investigate the catalytic activity of single and double dopant of boron (B), nitrogen (N), and phosphorous (P) anchored on diamond surfaces for the CO2 reduction reaction (CO2RR) by analyzing reaction energy profiles. Our findings show that the double-doped catalyst exhibits lower energy barriers in CO2RR compared to the single dopants. Specifically, when considering BB and NN configurations, there is a thermodynamic preference towards the formation of formic acid (HCOOH) with overpotentials of 0.40 and 0.09 V, respectively. The co-doped catalyst comprising B and N (BN) demonstrates a tendency towards the formation of HCOOH without requiring any applied overpotentials. Notably, BN outperforms other catalysts, occupying the top position on the volcano plot, indicating the lowest limiting potential (UL), remarkable thermal stability, and the ability to suppress the competing hydrogen evolution reaction (HER). This research provides valuable insights into the product differentiation in the electroreduction of CO2. © 2023, The Authors. All rights reserved.

关键词： Density functional theory

General framework for the mechanical response of metallic glasses during strain-rate-dependent uniaxial compression

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Physical Review Materials 2023年第10期7卷 105604-105604页

作者： Weiwei Jin Amit Datye Udo D. Schwarz Mark D. Shattuck Corey S. O'Hern Department of Mechanical Engineering and Materials Science Yale University New Haven Connecticut 06520 USA Department of Chemical and Environmental Engineering Yale University New Haven Connecticut 06520 USA Benjamin Levich Institute and Physics Department The City College of New York New York New York 10031 USA Department of Physics Yale University New Haven Connecticut 06520 USA Department of Applied Physics Yale University New Haven Connecticut 06520 USA Graduate Program in Computational Biology and Bioinformatics Yale University New Haven Connecticut 06520 USA

Experimental data on compressive strength σmax versus strain rate ɛ̇eng for metallic glasses undergoing uniaxial compression show varying strain rate sensitivity. For some metallic glasses, σmax decreases with increasing ɛ̇eng, while for others, σmax increases with increasing ɛ̇eng, and for certain alloys σmax versus ɛ̇eng is nonmonotonic. To understand their strain rate sensitivity, we conduct molecular dynamics simulations of metallic glasses undergoing uniaxial compression at finite strain rates and coupled to heat baths with a range of temperatures T0 and damping parameters b. In the T0→0 and b→0 limits, we find that the compressive strength σmax versus temperature T obeys a “chevron-shaped” scaling relation. In the low-strain-rate regime, σmax decreases linearly with increasing T, whereas σmax grows as a power law with decreasing T in the high-strain-rate regime. For T0>0, σmax(T) deviates from the scaling curve at low strain rates, but σmax(T) rejoins the scaling curve as the strain rate increases. Enhanced dissipation reduces compression-induced heating, which causes σmax(T) to deviate from the b→0 scaling behavior for intermediate strain rates, but σmax(T) converges to the high-strain-rate power-law scaling behavior at sufficiently high strain rates. Determining σmax(T) as a function of b and T0 provides a general framework for explaining the strain rate sensitivity of metallic glasses under compression.

关键词： Compressive strength Mechanical deformation Amorphous materials Metallic glasses Molecular dynamics

Ten simple rules for reproducible research in jupyter notebooks

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arXiv 2018年

作者： Rule, Adam Birmingham, Amanda Zuniga, Cristal Altintas, Ilkay Huang, Shih-Cheng Knight, Rob Moshiri, Niema Nguyen, Mai H. Rosenthal, Sara Brin Pérez, Fernando Rose, Peter W. Design Lab UC San Diego San DiegoCA United States Center for Computational Biology and Bioinformatics UC San Diego San DiegoCA United States Department of Pediatrics UC San Diego San DiegoCA United States Data Science Hub San Diego Supercomputer Center UC San Diego San DiegoCA United States Departments of Bioengineering and Computer Science and Engineering Center for Microbiome Innovation UC San Diego San DiegoCA United States Bioinformatics and Systems Biology Graduate Program UC San Diego San DiegoCA United States Department of Statistics Berkeley Institute for Data Science UC Berkeley Lawrence Berkeley National Laboratory BerkeleyCA United States Biomedical Informatics Graduate Program Stanford University StanfordCA United States

Reproducibility of computational studies is a hallmark of scientific methodology. It enables researchers to build with confidence on the methods and findings of others, reuse and extend computational pipelines, and thereby drive scientific progress. Since many experimental studies rely on computational analyses, biologists need guidance on how to set up and document reproducible data analyses or simulations. In this paper, we address several questions about reproducibility. For example, what are the technical and non-technical barriers to reproducible computational studies? What opportunities and challenges do computational notebooks offer to overcome some of these barriers? What tools are available and how can they be used effectively? We have developed a set of rules to serve as a guide to scientists with a specific focus on computational notebook systems, such as Jupyter Notebooks, which have become a tool of choice for many applications. Notebooks combine detailed workflows with narrative text and visualization of results. Combined with software repositories and open source licensing, notebooks are powerful tools for transparent, collaborative, reproducible, and reusable data analyses. Copyright © 2018, The Authors. All rights reserved.

关键词： Digital storage