Effects of altered backbone composition on the folding kinetics and mechanism of an ultrafast-folding protein

Santhouse, Jacqueline R.; Leung, Jeremy M. G.; Chong, Lillian T.; Horne, W. Seth

doi:10.1039/d3sc03976e

Cited by 3 publications

(3 citation statements)

References 52 publications

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“…Accessible plotting capabilities for many different data sets should facilitate data exploration and simulation monitoring to identify trends and relationships within both WE or cMD data. We note that WEDAP is already being used by the simulation community, ,, and we expect to continue maintenance and development in parallel with the WESTPA software package. We hope that WEDAP can eventually be adapted to benefit other enhanced sampling communities, ,− only a few of which have companion tools for data visualization …”

Section: Discussionmentioning

confidence: 99%

“…4,5 WESTPA is a highly scalable, interoperable software package for carrying out WE simulations, with successful applications to the simulation of protein−ligand unbinding, 6 protein−protein 7 or protein−DNA binding, 8 large-scale protein conformational rearrangements, 9 phase separation of lipid bilayers, 10 membrane permeability of drug-like molecules, 11 and protein folding. 12,13 To run a WE simulation, WESTPA initiates multiple weighted trajectories (N) in parallel from one or more initial conformations (bstates). The configurational space is typically divided into bins along a progress coordinate (pcoord) toward a target state (tstate).…”

Section: ■ Introductionmentioning

confidence: 99%

“…To characterize biological processes beyond the time scales of conventional molecular dynamics (cMD) simulations, various enhanced sampling methods have been developed, including the weighted ensemble (WE) path sampling strategy, , which can be carried out using the Weighted Ensemble Simulation Toolkit with the Parallelization and Analysis (WESTPA) software package. , WESTPA is a highly scalable, interoperable software package for carrying out WE simulations, with successful applications to the simulation of protein–ligand unbinding, protein–protein or protein–DNA binding, large-scale protein conformational rearrangements, phase separation of lipid bilayers, membrane permeability of drug-like molecules, and protein folding. , …”

Section: Introductionmentioning

confidence: 99%

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WEDAP: A Python Package for Streamlined Plotting of Molecular Simulation Data

Yang,

Chong

2024

J. Chem. Inf. Model.

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Given the growing interest in path sampling methods for extending the time scales of molecular dynamics (MD) simulations, there has been great interest in software tools that streamline the generation of plots for monitoring the progress of large-scale simulations. Here, we present the WEDAP Python package for simplifying the analysis of data generated from either conventional MD simulations or the weighted ensemble (WE) path sampling method, as implemented in the widely used WESTPA software package. WEDAP facilitates (i) the parsing of WE simulation data stored in highly compressed, hierarchical HDF5 files and (ii) incorporates trajectory weights from WE simulations into all generated plots. Our Python package consists of multiple user-friendly interfaces: a command-line interface, a graphical user interface, and a Python application programming interface. We demonstrate the plotting features of WEDAP through a series of examples using data from WE and conventional MD simulations that focus on the HIV-1 capsid protein's C-terminal domain dimer as a showcase system. The source code for WEDAP is freely available on GitHub at https://github.com/chonglab-pitt/wedap.

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Section: Discussionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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WEDAP: A Python Package for Streamlined Plotting of Molecular Simulation Data

Yang,

Chong

2024

J. Chem. Inf. Model.

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Backbone Modification in a Protein Hydrophobic Core

Lin,

Horne

2024

Chemistry A European J

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Targeted protein backbone modification can recreate tertiary structures reminiscent of folds found in nature on artificial scaffolds with improved biostability. Incorporation of altered monomers in such entities is typically limited to sites distant from the hydrophobic core to avoid potential disruptions to folding. This is limiting, as it is advantageous in some applications to incorporate artificial connectivity at buried sites. Here, we report an examination of protein backbone modification targeted specifically to hydrophobic core positions and its impacts on tertiary folded structure and fold stability. Different artificial monomer types are placed at core, core‐flanking, or solvent‐exposed positions in a compact three‐helix protein. Effects on structure and folding energetics are assessed by NMR spectroscopy and biophysical methods. Results show that artificial residues can be well accommodated in the hydrophobic core of a defined tertiary fold, with effects on stability only modestly larger than identical changes at solvent‐exposed sites. Collectively, these results provide new insights into folding behavior of protein‐like artificial chains as well as strategies for the design of such molecules.

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WEDAP: A Python Package for Streamlined Plotting of Molecular Simulation Data

Yang,

Chong

2024

Preprint

Self Cite

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Given the growing interest in path sampling methods for extending the timescales of molecular dynamics (MD) simulations, there has been great interest in software tools that streamline the generation of plots for monitoring the progress of large-scale simulations. Here, we present the WEDAP Python package for simplifying the analysis of data generated from either conventional MD simulations or the weighted ensemble (WE) path sampling method, as implemented in the widely used WESTPA software package. WEDAP facilitates (i) the parsing of WE simulation data stored in highly compressed, hierarchical HDF5 files, and (ii) incorporates trajectory weights from WE simulations into all generated plots. Our Python package consists of multiple user- friendly interfaces: a command-line interface, a graphical user interface, and a Python application programming interface. We demonstrate the plotting features of WEDAP through a series of examples using data from WE and conventional MD simulations that focus on the HIV-1 capsid protein C-terminal domain dimer as a showcase system. The source code for WEDAP is freely available on GitHub at https://github.com/chonglab- pitt/wedap.

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Effects of altered backbone composition on the folding kinetics and mechanism of an ultrafast-folding protein

Abstract: Analysis of folding rates and folding mechanism in tertiary structure mimetics reveals pronounced context-dependent effects of artificial backbone connectivity on the folding process.

Cited by 3 publications

References 52 publications

WEDAP: A Python Package for Streamlined Plotting of Molecular Simulation Data

WEDAP: A Python Package for Streamlined Plotting of Molecular Simulation Data

Backbone Modification in a Protein Hydrophobic Core

WEDAP: A Python Package for Streamlined Plotting of Molecular Simulation Data

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