Perspective: Coarse-grained models for biomolecular systems

2013 ◽  
Vol 139 (9) ◽  
pp. 090901 ◽  
Author(s):  
W. G. Noid
Keyword(s):  
Coarse Grained ◽  
Biomolecular Systems

Structure network analysis to gain insights into GPCR function

2016 ◽  
Vol 44 (2) ◽  
pp. 613-618 ◽  
Author(s):  
Francesca Fanelli ◽  
Angelo Felline ◽  
Francesco Raimondi ◽  
Michele Seeber
Keyword(s):  
G Protein ◽  
Normal Mode Analysis ◽  
Network Models ◽  
Md Simulations ◽  
G Protein Coupled Receptors ◽  
Coarse Grained ◽  
Mode Analysis ◽  
Biomolecular Systems ◽  
Retinal Chromophore ◽  
G Protein Coupled

G protein coupled receptors (GPCRs) are allosteric proteins whose functioning fundamentals are the communication between the two poles of the helix bundle. Protein structure network (PSN) analysis is one of the graph theory-based approaches currently used to investigate the structural communication in biomolecular systems. Information on system's dynamics can be provided by atomistic molecular dynamics (MD) simulations or coarse grained elastic network models paired with normal mode analysis (ENM–NMA). The present review article describes the application of PSN analysis to uncover the structural communication in G protein coupled receptors (GPCRs). Strategies to highlight changes in structural communication upon misfolding, dimerization and activation are described. Focus is put on the ENM–NMA-based strategy applied to the crystallographic structures of rhodopsin in its inactive (dark) and signalling active (meta II (MII)) states, highlighting changes in structure network and centrality of the retinal chromophore in differentiating the inactive and active states of the receptor.

scholarly journals Determination of Protein Structural Ensembles by Hybrid-Resolution SAXS Restrained Molecular Dynamics.

2019 ◽  
Author(s):  
Cristina Paissoni ◽  
Alexander Jussupow ◽  
Carlo Camilloni
Keyword(s):  
Dynamical Behavior ◽  
Computational Cost ◽  
Three Dimensional ◽  
Md Simulations ◽  
Coarse Grained ◽  
Conformational Ensemble ◽  
Biomolecular Systems ◽  
Conformational Ensembles ◽  
Independent Experimental Data

<div><div><div><p>SAXS experiments provide low-resolution but valuable information about the dynamics of biomolecular systems, which could be ideally integrated in MD simulations to accurately determine conformational ensembles of flexible proteins. The applicability of this strategy is hampered by the high computational cost required to calculate scattering intensities from three-dimensional structures. We previously presented a metainference-based hybrid resolution method that makes atomistic SAXS-restrained MD simulation feasible by adopting a coarse-grained approach to efficiently back-calculate scattering intensities; here, we extend this technique, applying it in the framework of multiple-replica simulations with the aim to investigate the dynamical behavior of flexible biomolecules. The efficacy of the method is assessed on the K63-diubiquitin multi-domain protein, showing that inclusion of SAXS-restraints is effective in generating reliable and heterogenous conformational ensemble, also improving the agreement with independent experimental data.</p></div></div></div>

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>

Divide-and-Conquer Based Adaptive Coarse Grained Simulation of RNA

2010 ◽  
Author(s):  
Mohammad Poursina ◽  
Kishor Bhalerao ◽  
Kurt Anderson
Keyword(s):  
Molecular Modeling ◽  
Degrees Of Freedom ◽  
Traditional Approach ◽  
Equations Of Motion ◽  
Critical Role ◽  
Divide And Conquer ◽  
Coarse Grained ◽  
Biomolecular Systems ◽  
Spatial And Temporal Scales ◽  
O 10

Molecular modeling has gained increasing importance in recent years for predicting important structural properties of large biomolecular systems such as RNA which play a critical role in various biological processes. Given the complexity of biopolymers and their interactions within living organisms, efficient and adaptive multi-scale modeling approaches are necessary if one is to reasonably perform computational studies of interest. These studies nominally involve multiple important physical phenomena occurring at different spatial and temporal scales. These systems are typically characterized by large number of degrees of freedom O(103) – O(107). The temporal domains range from sub-femto seconds (O(10−16)) associated with the small high frequency oscillations of individual tightly bonded atoms to milliseconds (O(10−3)) or greater for the larger scale conformational motion. The traditional approach for molecular modeling involved fully atomistic models which results in fully decoupled equations of motion. The problems with this approach are well documented in literature.

scholarly journals Determination of Protein Structural Ensembles by Hybrid-Resolution SAXS Restrained Molecular Dynamics.

2019 ◽  
Author(s):  
Cristina Paissoni ◽  
Alexander Jussupow ◽  
Carlo Camilloni
Keyword(s):  
Dynamical Behavior ◽  
Computational Cost ◽  
Three Dimensional ◽  
Md Simulations ◽  
Coarse Grained ◽  
Conformational Ensemble ◽  
Biomolecular Systems ◽  
Conformational Ensembles ◽  
Independent Experimental Data

<div><div><div><p>SAXS experiments provide low-resolution but valuable information about the dynamics of biomolecular systems, which could be ideally integrated into MD simulations to accurately determine conformational ensembles of flexible proteins. The applicability of this strategy is hampered by the high computational cost required to calculate scattering intensities from three-dimensional structures. We previously presented a hybrid resolution method that makes atomistic SAXS-restrained MD simulation feasible by adopting a coarse-grained approach to efficiently back-calculate scattering intensities; here, we extend this technique, applying it in the framework of metainference with the aim to investigate the dynamical behavior of flexible biomolecules. The efficacy of the method is assessed on the K63-diubiquitin, showing that the inclusion of SAXS-restraints is effective in generating a reliable conformational ensemble, improving the agreement with independent experimental data.</p></div></div></div>

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):  
Zika Virus ◽  
Packing Problem ◽  
Md Simulations ◽  
Coarse Grained ◽  
Test Case ◽  
Biomolecular Systems ◽  
Enveloped Virus ◽  
Anionic Phospholipids ◽  
Detailed Structural Analysis ◽  
Intracellular Compartments

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 some issues to be overcome 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 to prepare 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 multiscale scheme is well preserved along the simulation as evidenced from the radial distribution function of each constituent. The VLP stabilizes at approximately 0.5 ms 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. A rationale for a possible role of anionic phospholipids in stabilizing the envelope is introduced. The presented pipeline can be extrapolated to study other viral systems as well as intracellular compartments, paving the way to whole cell simulations.<br>

The multiscale challenge for biomolecular systems: coarse-grained modeling

2006 ◽  
Vol 32 (3-4) ◽  
pp. 211-218 ◽  
Author(s):  
J.-W. Chu ◽  
S. Izveko ◽  
G. A. Voth
Keyword(s):  
Coarse Grained ◽  
Biomolecular Systems

scholarly journals Determination of Protein Structural Ensembles by Hybrid-Resolution SAXS Restrained Molecular Dynamics.

2019 ◽  
Author(s):  
Cristina Paissoni ◽  
Alexander Jussupow ◽  
Carlo Camilloni
Keyword(s):  
Dynamical Behavior ◽  
Computational Cost ◽  
Three Dimensional ◽  
Md Simulations ◽  
Coarse Grained ◽  
Conformational Ensemble ◽  
Biomolecular Systems ◽  
Conformational Ensembles ◽  
Independent Experimental Data

<div><div><div><p>SAXS experiments provide low-resolution but valuable information about the dynamics of biomolecular systems, which could be ideally integrated into MD simulations to accurately determine conformational ensembles of flexible proteins. The applicability of this strategy is hampered by the high computational cost required to calculate scattering intensities from three-dimensional structures. We previously presented a hybrid resolution method that makes atomistic SAXS-restrained MD simulation feasible by adopting a coarse-grained approach to efficiently back-calculate scattering intensities; here, we extend this technique, applying it in the framework of metainference with the aim to investigate the dynamical behavior of flexible biomolecules. The efficacy of the method is assessed on the K63-diubiquitin, showing that the inclusion of SAXS-restraints is effective in generating a reliable conformational ensemble, improving the agreement with independent experimental data.</p></div></div></div>

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>

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