LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 8 of total 8

Search options

  1. Article ; Online: Molecular-dynamics simulations of macromolecular diffraction, part II: Analysis of protein crystal simulations.

    Wych, David C / Wall, Michael E

    Methods in enzymology

    2023  Volume 688, Page(s) 115–143

    Abstract: Molecular-dynamics (MD) simulations have contributed substantially to our understanding of protein structure and dynamics, yielding insights into many biological processes including protein folding, drug binding, and mechanisms of protein-protein ... ...

    Abstract Molecular-dynamics (MD) simulations have contributed substantially to our understanding of protein structure and dynamics, yielding insights into many biological processes including protein folding, drug binding, and mechanisms of protein-protein interactions. Much of what is known about protein structure comes from macromolecular crystallography (MX) experiments. MD simulations of protein crystals are useful in the study of MX because the simulations can be analyzed to calculate almost any crystallographic observable of interest, from atomic coordinates to structure factors and densities, B-factors, multiple conformations and their populations/occupancies, and diffuse scattering intensities. Computing resources and software to support crystalline MD simulations are now readily available to many researchers studying protein structure and dynamics and who may be interested in advanced interpretation of MX data, including diffuse scattering. In this work, we outline methods of analyzing MD simulations of protein crystals and provide accompanying Jupyter notebooks as practical resources for researchers wishing to perform similar analyses on their own systems of interest.
    MeSH term(s) Crystallography ; Macromolecular Substances ; Molecular Dynamics Simulation ; Protein Folding ; Software
    Chemical Substances Macromolecular Substances
    Language English
    Publishing date 2023-08-18
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1557-7988
    ISSN (online) 1557-7988
    DOI 10.1016/bs.mie.2023.06.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Molecular-dynamics simulations of macromolecular diffraction, part I: Preparation of protein crystal simulations.

    Wych, David C / Wall, Michael E

    Methods in enzymology

    2023  Volume 688, Page(s) 87–114

    Abstract: Molecular-dynamics (MD) simulations of protein crystals enable the prediction of structural and dynamical features of both the protein and the solvent components of macromolecular crystals, which can be validated against diffraction data from X-ray ... ...

    Abstract Molecular-dynamics (MD) simulations of protein crystals enable the prediction of structural and dynamical features of both the protein and the solvent components of macromolecular crystals, which can be validated against diffraction data from X-ray crystallographic experiments. The simulations have been useful for studying and predicting both Bragg and diffuse scattering in protein crystallography; however, the preparation is not yet automated and includes choices and tradeoffs that can impact the results. Here we examine some of the intricacies and consequences of the choices involved in setting up MD simulations of protein crystals for the study of diffraction data, and provide a recipe for preparing the simulations, packaged in an accompanying Jupyter notebook. This article and the accompanying notebook are intended to serve as practical resources for researchers wishing to put these models to work.
    MeSH term(s) Proteins/chemistry ; Molecular Dynamics Simulation ; Crystallography, X-Ray ; Solvents/chemistry ; X-Ray Diffraction
    Chemical Substances Proteins ; Solvents
    Language English
    Publishing date 2023-08-17
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1557-7988
    ISSN (online) 1557-7988
    DOI 10.1016/bs.mie.2023.06.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Molecular-dynamics simulation methods for macromolecular crystallography.

    Wych, David C / Aoto, Phillip C / Vu, Lily / Wolff, Alexander M / Mobley, David L / Fraser, James S / Taylor, Susan S / Wall, Michael E

    Acta crystallographica. Section D, Structural biology

    2023  Volume 79, Issue Pt 1, Page(s) 50–65

    Abstract: It is investigated whether molecular-dynamics (MD) simulations can be used to enhance macromolecular crystallography (MX) studies. Historically, protein crystal structures have been described using a single set of atomic coordinates. Because ... ...

    Abstract It is investigated whether molecular-dynamics (MD) simulations can be used to enhance macromolecular crystallography (MX) studies. Historically, protein crystal structures have been described using a single set of atomic coordinates. Because conformational variation is important for protein function, researchers now often build models that contain multiple structures. Methods for building such models can fail, however, in regions where the crystallographic density is difficult to interpret, for example at the protein-solvent interface. To address this limitation, a set of MD-MX methods that combine MD simulations of protein crystals with conventional modeling and refinement tools have been developed. In an application to a cyclic adenosine monophosphate-dependent protein kinase at room temperature, the procedure improved the interpretation of ambiguous density, yielding an alternative water model and a revised protein model including multiple conformations. The revised model provides mechanistic insights into the catalytic and regulatory interactions of the enzyme. The same methods may be used in other MX studies to seek mechanistic insights.
    MeSH term(s) Protein Conformation ; Molecular Dynamics Simulation ; Proteins/chemistry ; Solvents/chemistry ; Crystallography, X-Ray
    Chemical Substances Proteins ; Solvents
    Language English
    Publishing date 2023-01-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2968623-4
    ISSN 2059-7983 ; 0907-4449
    ISSN (online) 2059-7983
    ISSN 0907-4449
    DOI 10.1107/S2059798322011871
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Enhancing Sampling of Water Rehydration on Ligand Binding: A Comparison of Techniques.

    Ge, Yunhui / Wych, David C / Samways, Marley L / Wall, Michael E / Essex, Jonathan W / Mobley, David L

    Journal of chemical theory and computation

    2022  Volume 18, Issue 3, Page(s) 1359–1381

    Abstract: Water often plays a key role in protein structure, molecular recognition, and mediating protein-ligand interactions. Thus, free energy calculations must adequately sample water motions, which often proves challenging in typical MD simulation time scales. ...

    Abstract Water often plays a key role in protein structure, molecular recognition, and mediating protein-ligand interactions. Thus, free energy calculations must adequately sample water motions, which often proves challenging in typical MD simulation time scales. Thus, the accuracy of methods relying on MD simulations ends up limited by slow water sampling. Particularly, as a ligand is removed or modified, bulk water may not have time to fill or rearrange in the binding site. In this work, we focus on several molecular dynamics (MD) simulation-based methods attempting to help rehydrate buried water sites: BLUES, using nonequilibrium candidate Monte Carlo (NCMC);
    MeSH term(s) Binding Sites ; Fluid Therapy ; Ligands ; Molecular Dynamics Simulation ; Monte Carlo Method ; Protein Binding ; Thermodynamics ; Water/chemistry
    Chemical Substances Ligands ; Water (059QF0KO0R)
    Language English
    Publishing date 2022-02-11
    Publishing country United States
    Document type Journal Article
    ISSN 1549-9626
    ISSN (online) 1549-9626
    DOI 10.1021/acs.jctc.1c00590
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article: Liquid-like and rigid-body motions in molecular-dynamics simulations of a crystalline protein.

    Wych, David C / Fraser, James S / Mobley, David L / Wall, Michael E

    Structural dynamics (Melville, N.Y.)

    2019  Volume 6, Issue 6, Page(s) 64704

    Abstract: To gain insight into crystalline protein dynamics, we performed molecular-dynamics (MD) simulations of a periodic 2 × 2 × 2 supercell of staphylococcal nuclease. We used the resulting MD trajectories to simulate X-ray diffraction and to study collective ... ...

    Abstract To gain insight into crystalline protein dynamics, we performed molecular-dynamics (MD) simulations of a periodic 2 × 2 × 2 supercell of staphylococcal nuclease. We used the resulting MD trajectories to simulate X-ray diffraction and to study collective motions. The agreement of simulated X-ray diffraction with the data is comparable to previous MD simulation studies. We studied collective motions by analyzing statistically the covariance of alpha-carbon position displacements. The covariance decreases exponentially with the distance between atoms, which is consistent with a liquidlike motions (LLM) model, in which the protein behaves like a soft material. To gain finer insight into the collective motions, we examined the covariance behavior within a protein molecule (intraprotein) and between different protein molecules (interprotein). The interprotein atom pairs, which dominate the overall statistics, exhibit LLM behavior; however, the intraprotein pairs exhibit behavior that is consistent with a superposition of LLM and rigid-body motions (RBM). Our results indicate that LLM behavior of global dynamics is present in MD simulations of a protein crystal. They also show that RBM behavior is detectable in the simulations but that it is subsumed by the LLM behavior. Finally, the results provide clues about how correlated motions of atom pairs both within and across proteins might manifest in diffraction data. Overall, our findings increase our understanding of the connection between molecular motions and diffraction data and therefore advance efforts to extract information about functionally important motions from crystallography experiments.
    Language English
    Publishing date 2019-12-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2758684-4
    ISSN 2329-7778
    ISSN 2329-7778
    DOI 10.1063/1.5132692
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article ; Online: Water Networks in Photosystem II Using Crystalline Molecular Dynamics Simulations and Room-Temperature XFEL Serial Crystallography.

    Doyle, Margaret D / Bhowmick, Asmit / Wych, David C / Lassalle, Louise / Simon, Philipp S / Holton, James / Sauter, Nicholas K / Yachandra, Vittal K / Kern, Jan F / Yano, Junko / Wall, Michael E

    Journal of the American Chemical Society

    2023  Volume 145, Issue 27, Page(s) 14621–14635

    Abstract: Structural dynamics of water and its hydrogen-bonding networks play an important role in enzyme function via the transport of protons, ions, and substrates. To gain insights into these mechanisms in the water oxidation reaction in Photosystem II (PS II), ...

    Abstract Structural dynamics of water and its hydrogen-bonding networks play an important role in enzyme function via the transport of protons, ions, and substrates. To gain insights into these mechanisms in the water oxidation reaction in Photosystem II (PS II), we have performed crystalline molecular dynamics (MD) simulations of the dark-stable S
    Language English
    Publishing date 2023-06-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3155-0
    ISSN 1520-5126 ; 0002-7863
    ISSN (online) 1520-5126
    ISSN 0002-7863
    DOI 10.1021/jacs.3c01412
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Bonn / Germany

    Z 4' 55/32: Show issues
    Z 7.3: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  7. Article ; Online: Changes in an enzyme ensemble during catalysis observed by high-resolution XFEL crystallography.

    Smith, Nathan / Dasgupta, Medhanjali / Wych, David C / Dolamore, Cole / Sierra, Raymond G / Lisova, Stella / Marchany-Rivera, Darya / Cohen, Aina E / Boutet, Sébastien / Hunter, Mark S / Kupitz, Christopher / Poitevin, Frédéric / Moss, Frank R / Mittan-Moreau, David W / Brewster, Aaron S / Sauter, Nicholas K / Young, Iris D / Wolff, Alexander M / Tiwari, Virendra K /
    Kumar, Nivesh / Berkowitz, David B / Hadt, Ryan G / Thompson, Michael C / Follmer, Alec H / Wall, Michael E / Wilson, Mark A

    Science advances

    2024  Volume 10, Issue 13, Page(s) eadk7201

    Abstract: Enzymes populate ensembles of structures necessary for catalysis that are difficult to experimentally characterize. We use time-resolved mix-and-inject serial crystallography at an x-ray free electron laser to observe catalysis in a designed mutant ... ...

    Abstract Enzymes populate ensembles of structures necessary for catalysis that are difficult to experimentally characterize. We use time-resolved mix-and-inject serial crystallography at an x-ray free electron laser to observe catalysis in a designed mutant isocyanide hydratase (ICH) enzyme that enhances sampling of important minor conformations. The active site exists in a mixture of conformations, and formation of the thioimidate intermediate selects for catalytically competent substates. The influence of cysteine ionization on the ICH ensemble is validated by determining structures of the enzyme at multiple pH values. Large molecular dynamics simulations in crystallo and time-resolved electron density maps show that Asp
    MeSH term(s) Crystallography, X-Ray ; Proteins/chemistry ; Catalysis ; Molecular Dynamics Simulation ; Protein Conformation ; Hydrolases
    Chemical Substances Proteins ; Hydrolases (EC 3.-)
    Language English
    Publishing date 2024-03-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.adk7201
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  8. Article: Changes in an Enzyme Ensemble During Catalysis Observed by High Resolution XFEL Crystallography.

    Smith, Nathan / Dasgupta, Medhanjali / Wych, David C / Dolamore, Cole / Sierra, Raymond G / Lisova, Stella / Marchany-Rivera, Darya / Cohen, Aina E / Boutet, Sébastien / Hunter, Mark S / Kupitz, Christopher / Poitevin, Frédéric / Moss, Frank R / Brewster, Aaron S / Sauter, Nicholas K / Young, Iris D / Wolff, Alexander M / Tiwari, Virendra K / Kumar, Nivesh /
    Berkowitz, David B / Hadt, Ryan G / Thompson, Michael C / Follmer, Alec H / Wall, Michael E / Wilson, Mark A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Enzymes populate ensembles of structures with intrinsically different catalytic proficiencies that are difficult to experimentally characterize. We use time-resolved mix-and-inject serial crystallography (MISC) at an X-ray free electron laser (XFEL) to ... ...

    Abstract Enzymes populate ensembles of structures with intrinsically different catalytic proficiencies that are difficult to experimentally characterize. We use time-resolved mix-and-inject serial crystallography (MISC) at an X-ray free electron laser (XFEL) to observe catalysis in a designed mutant (G150T) isocyanide hydratase (ICH) enzyme that enhances sampling of important minor conformations. The active site exists in a mixture of conformations and formation of the thioimidate catalytic intermediate selects for catalytically competent substates. A prior proposal for active site cysteine charge-coupled conformational changes in ICH is validated by determining structures of the enzyme over a range of pH values. A combination of large molecular dynamics simulations of the enzyme in crystallo and time-resolved electron density maps shows that ionization of the general acid Asp17 during catalysis causes additional conformational changes that propagate across the dimer interface, connecting the two active sites. These ionization-linked changes in the ICH conformational ensemble permit water to enter the active site in a location that is poised for intermediate hydrolysis. ICH exhibits a tight coupling between ionization of active site residues and catalysis-activated protein motions, exemplifying a mechanism of electrostatic control of enzyme dynamics.
    Language English
    Publishing date 2023-08-16
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.08.15.553460
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top