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Web-based computational chemistry education with CHARMMing II: Coarse-grained protein folding.

Pickard FC, Miller BT, Schalk V, Lerner MG, Woodcock HL, Brooks BR - PLoS Comput. Biol. (2014)

Bottom Line: As a proof of concept, this lesson demonstrates the construction of a CG model of a small globular protein, its simulation via Langevin dynamics, and the analysis of the resulting data.New functionality has been added to CHARMMing to facilitate this process.The implementation of these features into CHARMMing helps automate many of the tedious aspects of constructing a CG Gō model.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

ABSTRACT
A lesson utilizing a coarse-grained (CG) Gō-like model has been implemented into the CHARMM INterface and Graphics (CHARMMing) web portal (www.charmming.org) to the Chemistry at HARvard Macromolecular Mechanics (CHARMM) molecular simulation package. While widely used to model various biophysical processes, such as protein folding and aggregation, CG models can also serve as an educational tool because they can provide qualitative descriptions of complex biophysical phenomena for a relatively cheap computational cost. As a proof of concept, this lesson demonstrates the construction of a CG model of a small globular protein, its simulation via Langevin dynamics, and the analysis of the resulting data. This lesson makes connections between modern molecular simulation techniques and topics commonly presented in an advanced undergraduate lecture on physical chemistry. It culminates in a straightforward analysis of a short dynamics trajectory of a small fast folding globular protein; we briefly describe the thermodynamic properties that can be calculated from this analysis. The assumptions inherent in the model and the data analysis are laid out in a clear, concise manner, and the techniques used are consistent with those employed by specialists in the field of CG modeling. One of the major tasks in building the Gō-like model is determining the relative strength of the nonbonded interactions between coarse-grained sites. New functionality has been added to CHARMMing to facilitate this process. The implementation of these features into CHARMMing helps automate many of the tedious aspects of constructing a CG Gō model. The CG model builder and its accompanying lesson should be a valuable tool to chemistry students, teachers, and modelers in the field.

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The native structure of the GA module of an albumin binding domain.Three representations of the structure are shown. The left panel shows the backbone of the native fold as a ribbon, which highlights the helical nature of the secondary structure. The center panel shows the AA structure, which is used to build the KT G model (right panel).
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pcbi-1003738-g001: The native structure of the GA module of an albumin binding domain.Three representations of the structure are shown. The left panel shows the backbone of the native fold as a ribbon, which highlights the helical nature of the secondary structure. The center panel shows the AA structure, which is used to build the KT G model (right panel).

Mentions: Computer models can be constructed at a variety of scales or resolutions (Figure 1). Many simulation techniques represent each atom as a single interaction center. The interactions between beads can then be evaluated using a force field. However, it is possible to construct a coarse-grained (CG) model, in which multiple atoms are represented by a single center (as in the right-hand panel of Figure 1). These types of models can be useful theoretical tools because they can be specifically designed for a system or process of interest. By providing a simplified view of a complex molecular process, important physical details are retained in the model, while superfluous details are ignored. The resulting CG model distills the essence of the biophysical process into its most important physical details, allowing the computational scientist a fundamental understanding of the process.


Web-based computational chemistry education with CHARMMing II: Coarse-grained protein folding.

Pickard FC, Miller BT, Schalk V, Lerner MG, Woodcock HL, Brooks BR - PLoS Comput. Biol. (2014)

The native structure of the GA module of an albumin binding domain.Three representations of the structure are shown. The left panel shows the backbone of the native fold as a ribbon, which highlights the helical nature of the secondary structure. The center panel shows the AA structure, which is used to build the KT G model (right panel).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109841&req=5

pcbi-1003738-g001: The native structure of the GA module of an albumin binding domain.Three representations of the structure are shown. The left panel shows the backbone of the native fold as a ribbon, which highlights the helical nature of the secondary structure. The center panel shows the AA structure, which is used to build the KT G model (right panel).
Mentions: Computer models can be constructed at a variety of scales or resolutions (Figure 1). Many simulation techniques represent each atom as a single interaction center. The interactions between beads can then be evaluated using a force field. However, it is possible to construct a coarse-grained (CG) model, in which multiple atoms are represented by a single center (as in the right-hand panel of Figure 1). These types of models can be useful theoretical tools because they can be specifically designed for a system or process of interest. By providing a simplified view of a complex molecular process, important physical details are retained in the model, while superfluous details are ignored. The resulting CG model distills the essence of the biophysical process into its most important physical details, allowing the computational scientist a fundamental understanding of the process.

Bottom Line: As a proof of concept, this lesson demonstrates the construction of a CG model of a small globular protein, its simulation via Langevin dynamics, and the analysis of the resulting data.New functionality has been added to CHARMMing to facilitate this process.The implementation of these features into CHARMMing helps automate many of the tedious aspects of constructing a CG Gō model.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

ABSTRACT
A lesson utilizing a coarse-grained (CG) Gō-like model has been implemented into the CHARMM INterface and Graphics (CHARMMing) web portal (www.charmming.org) to the Chemistry at HARvard Macromolecular Mechanics (CHARMM) molecular simulation package. While widely used to model various biophysical processes, such as protein folding and aggregation, CG models can also serve as an educational tool because they can provide qualitative descriptions of complex biophysical phenomena for a relatively cheap computational cost. As a proof of concept, this lesson demonstrates the construction of a CG model of a small globular protein, its simulation via Langevin dynamics, and the analysis of the resulting data. This lesson makes connections between modern molecular simulation techniques and topics commonly presented in an advanced undergraduate lecture on physical chemistry. It culminates in a straightforward analysis of a short dynamics trajectory of a small fast folding globular protein; we briefly describe the thermodynamic properties that can be calculated from this analysis. The assumptions inherent in the model and the data analysis are laid out in a clear, concise manner, and the techniques used are consistent with those employed by specialists in the field of CG modeling. One of the major tasks in building the Gō-like model is determining the relative strength of the nonbonded interactions between coarse-grained sites. New functionality has been added to CHARMMing to facilitate this process. The implementation of these features into CHARMMing helps automate many of the tedious aspects of constructing a CG Gō model. The CG model builder and its accompanying lesson should be a valuable tool to chemistry students, teachers, and modelers in the field.

Show MeSH