The Experts below are selected from a list of 33186 Experts worldwide ranked by ideXlab platform

Gregory A Voth - One of the best experts on this subject based on the ideXlab platform.

  • a multiscale Coarse Grained Model of the sars cov 2 virion
    Biophysical Journal, 2021
    Co-Authors: Alexander J Pak, Viviana Monjegalvan, Lorenzo Casalino, Zied Gaieb, Abigail C Dommer, Rommie E Amaro, Gregory A Voth
    Abstract:

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Computer simulations of complete viral particles can provide theoretical insights into large-scale viral processes including assembly, budding, egress, entry, and fusion. Detailed atomistic simulations are constrained to shorter timescales and require billion-atom simulations for these processes. Here, we report the current status and ongoing development of a largely "bottom-up" Coarse-Grained (CG) Model of the SARS-CoV-2 virion. Data from a combination of cryo-electron microscopy (cryo-EM), x-ray crystallography, and computational predictions were used to build molecular Models of structural SARS-CoV-2 proteins, which were then assembled into a complete virion Model. We describe how CG molecular interactions can be derived from all-atom simulations, how viral behavior difficult to capture in atomistic simulations can be incorporated into the CG Models, and how the CG Models can be iteratively improved as new data become publicly available. Our initial CG Model and the detailed methods presented are intended to serve as a resource for researchers working on COVID-19 who are interested in performing multiscale simulations of the SARS-CoV-2 virion.

  • Coarse Grained force fields from the perspective of statistical mechanics better understanding of the origins of a martini hangover
    Journal of Chemical Theory and Computation, 2021
    Co-Authors: Zack Jarin, James Newhouse, Gregory A Voth
    Abstract:

    The popular MARTINI Coarse-Grained Model is used as a test case to analyze the adherence of top-down Coarse-Grained molecular dynamics Models (i.e., Models primarily parametrized to match experimen...

  • a multiscale Coarse Grained Model of the sars cov 2 virion
    bioRxiv, 2020
    Co-Authors: Alexander J Pak, Viviana Monjegalvan, Lorenzo Casalino, Zied Gaieb, Abigail C Dommer, Rommie E Amaro, Gregory A Voth
    Abstract:

    Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Computer simulations of complete viral particles can provide theoretical insights into large-scale viral processes including assembly, budding, egress, entry, and fusion. Detailed atomistic simulations, however, are constrained to shorter timescales and require billion-atom simulations for these processes. Here, we report the current status and on-going development of a largely “bottom-up” Coarse-Grained (CG) Model of the SARS-CoV-2 virion. Structural data from a combination of cryo-electron microscopy (cryo-EM), x-ray crystallography, and computational predictions were used to build molecular Models of structural SARS-CoV-2 proteins, which were then assembled into a complete virion Model. We describe how CG molecular interactions can be derived from all-atom simulations, how viral behavior difficult to capture in atomistic simulations can be incorporated into the CG Models, and how the CG Models can be iteratively improved as new data becomes publicly available. Our initial CG Model and the detailed methods presented are intended to serve as a resource for researchers working on COVID-19 who are interested in performing multiscale simulations of the SARS-CoV-2 virion. Significance Statement This study reports the construction of a molecular Model for the SARS-CoV-2 virion and details our multiscale approach towards Model refinement. The resulting Model and methods can be applied to and enable the simulation of SARS-CoV-2 virions.

Daan Frenkel - One of the best experts on this subject based on the ideXlab platform.

  • Modelling aggregates of cetyltrimethylammonium bromide on gold surfaces using dissipative particle dynamics simulations
    Molecular Simulation, 2021
    Co-Authors: Yawei Liu, Jiachen Wei, Daan Frenkel, Asaph Widmercooper
    Abstract:

    In this study, we developed a Coarse-Grained Model based on the dissipative particle dynamics (DPD) method to investigate the aggregates of the cetyltrimethylammonium bromide (CTAB) molecules on go...

  • procedure to construct a multi scale Coarse Grained Model of dna coated colloids from experimental data
    Soft Matter, 2013
    Co-Authors: Julia Fornleitner, Bianca M. Mladek, Alexandre Dawid, Francisco J Martinezveracoechea, Daan Frenkel
    Abstract:

    We present a quantitative, multi-scale Coarse-Grained Model of DNA coated colloids. The parameters of this Model are transferable and are solely based on experimental data. As a test case, we focus on nano-sized colloids carrying single-stranded DNA of length comparable to the colloids' size. We show that in this regime, the common theoretical approach of assuming pairwise additivity of the colloidal pair interactions leads to quantitatively and sometimes even qualitatively wrong predictions of the phase behaviour of DNA-grafted colloids. Compared to experimental data, we find that our Coarse-Grained Model correctly predicts the equilibrium structure and melting temperature of the formed solids. Due to limited experimental information on the persistence length of single-stranded DNA, some quantitative discrepancies are found in the prediction of spatial quantities. With the availability of better experimental data, the present approach provides a path for the rational design of DNA-functionalised building blocks that can self-assemble into complex, three-dimensional structures.

  • Procedure to construct a multi-scale Coarse-Grained Model of DNA-coated colloids from experimental data
    Soft Matter, 2013
    Co-Authors: Bianca M. Mladek, Julia Fornleitner, Francisco J. Martinez-veracoechea, Alexandre Dawid, Daan Frenkel
    Abstract:

    We present a quantitative, multi-scale Coarse-Grained Model of DNA coated colloids. The parameters of this Model are transferable and are solely based on experimental data. As a test case, we focus on nano-sized colloids carrying single-stranded DNA strands of length comparable to the colloids' size. We show that in this regime, the common theoretical approach of assuming pairwise additivity of the colloidal pair interactions leads to quantitatively and sometimes even qualitatively wrong predictions of the phase behaviour of DNA-grafted colloids. Comparing to experimental data, we find that our Coarse-Grained Model correctly predicts the equilibrium structure and melting temperature of the formed solids. Due to limited experimental information on the persistence length of single-stranded DNA, some quantitative discrepancies are found in the prediction of spatial quantities. With the availability of better experimental data, the present approach provides a path for the rational design of DNA-functionalised building blocks that can self-assemble in complex, three-dimensional structures.

Bianca M. Mladek - One of the best experts on this subject based on the ideXlab platform.

  • procedure to construct a multi scale Coarse Grained Model of dna coated colloids from experimental data
    Soft Matter, 2013
    Co-Authors: Julia Fornleitner, Bianca M. Mladek, Alexandre Dawid, Francisco J Martinezveracoechea, Daan Frenkel
    Abstract:

    We present a quantitative, multi-scale Coarse-Grained Model of DNA coated colloids. The parameters of this Model are transferable and are solely based on experimental data. As a test case, we focus on nano-sized colloids carrying single-stranded DNA of length comparable to the colloids' size. We show that in this regime, the common theoretical approach of assuming pairwise additivity of the colloidal pair interactions leads to quantitatively and sometimes even qualitatively wrong predictions of the phase behaviour of DNA-grafted colloids. Compared to experimental data, we find that our Coarse-Grained Model correctly predicts the equilibrium structure and melting temperature of the formed solids. Due to limited experimental information on the persistence length of single-stranded DNA, some quantitative discrepancies are found in the prediction of spatial quantities. With the availability of better experimental data, the present approach provides a path for the rational design of DNA-functionalised building blocks that can self-assemble into complex, three-dimensional structures.

  • Procedure to construct a multi-scale Coarse-Grained Model of DNA-coated colloids from experimental data
    Soft Matter, 2013
    Co-Authors: Bianca M. Mladek, Julia Fornleitner, Francisco J. Martinez-veracoechea, Alexandre Dawid, Daan Frenkel
    Abstract:

    We present a quantitative, multi-scale Coarse-Grained Model of DNA coated colloids. The parameters of this Model are transferable and are solely based on experimental data. As a test case, we focus on nano-sized colloids carrying single-stranded DNA strands of length comparable to the colloids' size. We show that in this regime, the common theoretical approach of assuming pairwise additivity of the colloidal pair interactions leads to quantitatively and sometimes even qualitatively wrong predictions of the phase behaviour of DNA-grafted colloids. Comparing to experimental data, we find that our Coarse-Grained Model correctly predicts the equilibrium structure and melting temperature of the formed solids. Due to limited experimental information on the persistence length of single-stranded DNA, some quantitative discrepancies are found in the prediction of spatial quantities. With the availability of better experimental data, the present approach provides a path for the rational design of DNA-functionalised building blocks that can self-assemble in complex, three-dimensional structures.

Andrew J Mccammon - One of the best experts on this subject based on the ideXlab platform.

  • flap opening dynamics in hiv 1 protease explored with a Coarse Grained Model
    Journal of Structural Biology, 2007
    Co-Authors: Valentina Tozzini, Joanna Trylska, Chiaen A Chang, Andrew J Mccammon
    Abstract:

    We present a one-bead Coarse-Grained Model that enables dynamical simulations of proteins on the time scale of tens of microseconds. The parameterization of the force field includes accurate conformational terms that allow for fast and reliable exploration of the configurational space. The Model is applied to the dynamics of flap opening in HIV-1 protease. The experimental structure of the recently crystallized semi-open conformation of HIV-1 protease is well reproduced in the simulation, which supports the accuracy of our Model. Thanks to very long simulations and extensive sampling of opening and closing events, we also investigate the thermodynamics and kinetics of the opening process. We have shown that the effect of the solvent slows down the dynamics to the experimentally observed time scales. The Model is found to be reliable for application to substrate docking simulations, which are currently in progress.

  • a Coarse Grained Model for the dynamics of flap opening in hiv 1 protease
    Chemical Physics Letters, 2005
    Co-Authors: Valentina Tozzini, Andrew J Mccammon
    Abstract:

    Abstract A Coarse Grained Model for proteins is developed and applied to HIV-1 protease. Molecular dynamics simulations on the μsec timescale and the use of a flexible force field allow study of the opening of the ‘flaps’ protecting the active site. The opening mechanism reveals peculiar features that might be involved in the substrate capture. An allosteric inhibition effect is demonstrated in specific regions of the protein. This study indicates alternative conformations and target sites to be used as basis for the design of novel inhibitor drugs.

Valentina Tozzini - One of the best experts on this subject based on the ideXlab platform.

  • flap opening dynamics in hiv 1 protease explored with a Coarse Grained Model
    Journal of Structural Biology, 2007
    Co-Authors: Valentina Tozzini, Joanna Trylska, Chiaen A Chang, Andrew J Mccammon
    Abstract:

    We present a one-bead Coarse-Grained Model that enables dynamical simulations of proteins on the time scale of tens of microseconds. The parameterization of the force field includes accurate conformational terms that allow for fast and reliable exploration of the configurational space. The Model is applied to the dynamics of flap opening in HIV-1 protease. The experimental structure of the recently crystallized semi-open conformation of HIV-1 protease is well reproduced in the simulation, which supports the accuracy of our Model. Thanks to very long simulations and extensive sampling of opening and closing events, we also investigate the thermodynamics and kinetics of the opening process. We have shown that the effect of the solvent slows down the dynamics to the experimentally observed time scales. The Model is found to be reliable for application to substrate docking simulations, which are currently in progress.

  • a Coarse Grained Model for the dynamics of flap opening in hiv 1 protease
    Chemical Physics Letters, 2005
    Co-Authors: Valentina Tozzini, Andrew J Mccammon
    Abstract:

    Abstract A Coarse Grained Model for proteins is developed and applied to HIV-1 protease. Molecular dynamics simulations on the μsec timescale and the use of a flexible force field allow study of the opening of the ‘flaps’ protecting the active site. The opening mechanism reveals peculiar features that might be involved in the substrate capture. An allosteric inhibition effect is demonstrated in specific regions of the protein. This study indicates alternative conformations and target sites to be used as basis for the design of novel inhibitor drugs.