- Force-Field Representation of Biomolecular Systems

2015 ◽  
pp. 62-95 ◽  
Keyword(s):  
Force Field ◽  
Biomolecular Systems ◽  
Field Representation

scholarly journals Wrapping up Viruses at Multiscale Resolution: Optimizing PACKMOL and SIRAH Execution for Simulating the Zika Virus.

2020 ◽  
Author(s):  
Martín Soñora ◽  
Leandro Martinez ◽  
Sergio Pantano ◽  
Matías R. Machado
Keyword(s):  
Force Field ◽  
Zika Virus ◽  
Packing Problem ◽  
Md Simulations ◽  
Coarse Grained ◽  
Test Case ◽  
Biomolecular Systems ◽  
Enveloped Virus ◽  
Anionic Phospholipids ◽  
Detailed Structural Analysis

<p> Simulating huge biomolecular complexes of million atoms at relevant biological timescales is becoming accessible to the broad scientific community. That proves to be crucial for urgent responses against emergent diseases in real time. Yet, there are still issues to sort regarding the system setup so that Molecular Dynamics (MD) simulations can be run in a simple and standard way. Here, we introduce an optimized pipeline for building and simulating enveloped virus-like particles (VLP). First, the membrane packing problem is tackled with new features and optimized options in PACKMOL. This allows preparing accurate membrane models of thousands of lipids in the context of a VLP within a few hours using a single CPU. Then, the assembly of the VLP system is done within the multiscale framework of the coarse-grained SIRAH force field. Finally, the equilibration protocol provides a system ready for production MD simulations within a few days on broadly accessible GPU resources. The pipeline is applied to study the Zika Virus as a test case for large biomolecular systems. The VLP stabilizes at approximately 0.5 microseconds of MD simulation, reproducing correlations greater than 0.90 against experimental density maps from cryo-electron microscopy. Detailed structural analysis of the protein envelope also shows very good agreement in root mean square deviations and B-factors with the experimental data. The level of details attained shows for the first time a possible role of anionic phospholipids in stabilizing the envelope. Combining an efficient and reliable setup procedure with an accurate coarse-grained force field provides a valuable pipeline for simulating arbitrary viral systems or sub-cellular compartments, paving the way towards whole-cell simulations.</p>

scholarly journals Wrapping up Viruses at Multiscale Resolution: Optimizing PACKMOL and SIRAH Execution for Simulating the Zika Virus.

2020 ◽  
Author(s):  
Martín Soñora ◽  
Leandro Martinez ◽  
Sergio Pantano ◽  
Matías R. Machado
Keyword(s):  
Force Field ◽  
Zika Virus ◽  
Packing Problem ◽  
Md Simulations ◽  
Coarse Grained ◽  
Test Case ◽  
Biomolecular Systems ◽  
Enveloped Virus ◽  
Anionic Phospholipids ◽  
Detailed Structural Analysis

<p> Simulating huge biomolecular complexes of million atoms at relevant biological timescales is becoming accessible to the broad scientific community. That proves to be crucial for urgent responses against emergent diseases in real time. Yet, there are still issues to sort regarding the system setup so that Molecular Dynamics (MD) simulations can be run in a simple and standard way. Here, we introduce an optimized pipeline for building and simulating enveloped virus-like particles (VLP). First, the membrane packing problem is tackled with new features and optimized options in PACKMOL. This allows preparing accurate membrane models of thousands of lipids in the context of a VLP within a few hours using a single CPU. Then, the assembly of the VLP system is done within the multiscale framework of the coarse-grained SIRAH force field. Finally, the equilibration protocol provides a system ready for production MD simulations within a few days on broadly accessible GPU resources. The pipeline is applied to study the Zika Virus as a test case for large biomolecular systems. The VLP stabilizes at approximately 0.5 microseconds of MD simulation, reproducing correlations greater than 0.90 against experimental density maps from cryo-electron microscopy. Detailed structural analysis of the protein envelope also shows very good agreement in root mean square deviations and B-factors with the experimental data. The level of details attained shows for the first time a possible role of anionic phospholipids in stabilizing the envelope. Combining an efficient and reliable setup procedure with an accurate coarse-grained force field provides a valuable pipeline for simulating arbitrary viral systems or sub-cellular compartments, paving the way towards whole-cell simulations.</p>

Improving force field accuracy by training against condensed phase mixture properties

2021 ◽  
Author(s):  
Simon Boothroyd ◽  
Owen Madin ◽  
David Mobley ◽  
Lee-Ping Wang ◽  
John Chodera ◽  
...  
Keyword(s):  
Force Field ◽  
Physical Property ◽  
Liquid Mixtures ◽  
Pure Liquid ◽  
Full Potential ◽  
Field Representation ◽  
Biological Phenomena ◽  
Liquid Systems ◽  
Fundamental Insight ◽  
Physical Property Data

Developing a sufficiently accurate classical force field representation of molecules is key to realizing the full potential of molecular simulation as a route to gaining fundamental insight into a broad spectrum of chemical and biological phenomena. This is only possible, however, if the many complex interactions between molecules of different species in the system are accurately captured by the model. Historically, the intermolecular van der Waals (vdW) interactions have primarily been trained against densities and enthalpies of vaporization of pure (single-component) systems, with occasional usage of hydration free energies. In this study, we demonstrate how including physical property data of binary mixtures can better inform these parameters, encoding more information about the underlying physics of the system in complex chemical mixtures. To demonstrate this, we re-train a select number of the Lennard-Jones parameters describing the vdW interactions of the OpenFF 1.0.0 (Parsley) fixed charge force field against training sets composed of densities and enthalpies of mixing for binary liquid mixtures as well as densities and enthalpies of vaporization of pure liquid systems, and assess the performance of each of these combinations. We show that retraining against the mixture data almost universally improves the force field's ability to reproduce both pure and mixture properties, reducing some systematic errors that exist when training vdW interactions against properties of pure systems only.

scholarly journals Improving force field accuracy by training against condensed phase mixture properties

2021 ◽  
Author(s):  
Simon Boothroyd ◽  
Owen Madin ◽  
David Mobley ◽  
Lee-Ping Wang ◽  
John Chodera ◽  
...  
Keyword(s):  
Force Field ◽  
Physical Property ◽  
Liquid Mixtures ◽  
Pure Liquid ◽  
Full Potential ◽  
Field Representation ◽  
Biological Phenomena ◽  
Liquid Systems ◽  
Fundamental Insight ◽  
Physical Property Data

Developing a sufficiently accurate classical force field representation of molecules is key to realizing the full potential of molecular simulation as a route to gaining fundamental insight into a broad spectrum of chemical and biological phenomena. This is only possible, however, if the many complex interactions between molecules of different species in the system are accurately captured by the model. Historically, the intermolecular van der Waals (vdW) interactions have primarily been trained against densities and enthalpies of vaporization of pure (single-component) systems, with occasional usage of hydration free energies. In this study, we demonstrate how including physical property data of binary mixtures can better inform these parameters, encoding more information about the underlying physics of the system in complex chemical mixtures. To demonstrate this, we re-train a select number of the Lennard-Jones parameters describing the vdW interactions of the OpenFF 1.0.0 (Parsley) fixed charge force field against training sets composed of densities and enthalpies of mixing for binary liquid mixtures as well as densities and enthalpies of vaporization of pure liquid systems, and assess the performance of each of these combinations. We show that retraining against the mixture data almost universally improves the force field's ability to reproduce both pure and mixture properties, reducing some systematic errors that exist when training vdW interactions against properties of pure systems only.

scholarly journals Static force field representation of environments based on agents’ nonlinear motions

2017 ◽  
Vol 2017 (1) ◽  
Author(s):  
Damian Campo ◽  
Alejandro Betancourt ◽  
Lucio Marcenaro ◽  
Carlo Regazzoni
Keyword(s):  
Force Field ◽  
Static Force ◽  
Field Representation ◽  
Nonlinear Motions
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