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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 workflow of the KT G  model lesson.Blue boxes represent the steps described in the text. Yellow boxes show the inputs and outputs of each step. Note that the CHARMM protein structure file is only built when a calculation is performed (minimization, in this case). Q is the fraction of native contacts as defined in the text.
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pcbi-1003738-g004: The workflow of the KT G model lesson.Blue boxes represent the steps described in the text. Yellow boxes show the inputs and outputs of each step. Note that the CHARMM protein structure file is only built when a calculation is performed (minimization, in this case). Q is the fraction of native contacts as defined in the text.

Mentions: In this lesson, we consider the protein G related albumin-binding domain (PDB code: 1PRB). This is a small globular protein that has been extensively studied, both experimentally and theoretically [37]–[39]. Experiment has shown that this protein folds near the semi-empirical speed limit of [40]. In solution, 1PRB forms a three-helix bundle (Figure 1); it readily interconverts between its folded and unfolded states, allowing rapid convergence of its thermodynamic properties. These features, taken together, make it an ideal candidate to demonstrate the efficacy of CG methodologies in an educational environment. The sequence of steps that are carried out by the lesson, along with their inputs and outputs, are shown in Figure 4.


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 workflow of the KT G  model lesson.Blue boxes represent the steps described in the text. Yellow boxes show the inputs and outputs of each step. Note that the CHARMM protein structure file is only built when a calculation is performed (minimization, in this case). Q is the fraction of native contacts as defined in the text.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1003738-g004: The workflow of the KT G model lesson.Blue boxes represent the steps described in the text. Yellow boxes show the inputs and outputs of each step. Note that the CHARMM protein structure file is only built when a calculation is performed (minimization, in this case). Q is the fraction of native contacts as defined in the text.
Mentions: In this lesson, we consider the protein G related albumin-binding domain (PDB code: 1PRB). This is a small globular protein that has been extensively studied, both experimentally and theoretically [37]–[39]. Experiment has shown that this protein folds near the semi-empirical speed limit of [40]. In solution, 1PRB forms a three-helix bundle (Figure 1); it readily interconverts between its folded and unfolded states, allowing rapid convergence of its thermodynamic properties. These features, taken together, make it an ideal candidate to demonstrate the efficacy of CG methodologies in an educational environment. The sequence of steps that are carried out by the lesson, along with their inputs and outputs, are shown in Figure 4.

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