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Title: Using a Coarse-Grained Modeling Framework to Identify Oligomeric Motifs with Tunable Secondary Structure

Abstract

Coarse-grained modeling can be used to explore general theories that are independent of specific chemical detail. In this paper, we present cg_openmm, a Python-based simulation framework for modeling coarse-grained hetero-oligomers and screening them for structural and thermodynamic characteristics of cooperative secondary structures. cg_openmm facilitates the building of coarse-grained topology and random starting configurations, setup of GPU-accelerated replica exchange molecular dynamics simulations with the OpenMM software package, and features a suite of postprocessing thermodynamic and structural analysis tools. In particular, native contact analysis, heat capacity calculations, and free energy of folding calculations are used to identify and characterize cooperative folding transitions and stable secondary structures. In this work, we demonstrate the capabilities of cg_openmm on a simple 1–1 Lennard-Jones coarse-grained model, in which each residue contains 1 backbone and 1 side-chain bead. By scanning both nonbonded and bonded force-field parameter spaces at the coarse-grained level, we identify and characterize sets of parameters which result in the formation of stable helices through cooperative folding transitions. Furthermore, we show that the geometries and stabilities of these helices can be tuned by manipulating the force-field parameters.

Authors:
ORCiD logo [1];  [1]; ORCiD logo [1]; ORCiD logo [1]
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  1. Univ. of Colorado, Boulder, CO (United States)
Publication Date:
Research Org.:
Univ. of Colorado, Boulder, CO (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1899344
Alternate Identifier(s):
OSTI ID: 1839292
Grant/Contract Number:  
SC0018651
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Chemical Theory and Computation
Additional Journal Information:
Journal Volume: 17; Journal Issue: 10; Related Information: https://github.com/shirtsgroup/cg_openmm; Journal ID: ISSN 1549-9618
Publisher:
American Chemical Society
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; switchable; foldamers; thermodynamics; cooperativity; folding; mathematical methods; stability; heat capacity

Citation Formats

Walker, Christopher C., Meek, Garrett A., Fobe, Theodore L., and Shirts, Michael R. Using a Coarse-Grained Modeling Framework to Identify Oligomeric Motifs with Tunable Secondary Structure. United States: N. p., 2021. Web. doi:10.1021/acs.jctc.1c00528.
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Walker, Christopher C., Meek, Garrett A., Fobe, Theodore L., & Shirts, Michael R. Using a Coarse-Grained Modeling Framework to Identify Oligomeric Motifs with Tunable Secondary Structure. United States. https://doi.org/10.1021/acs.jctc.1c00528
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Walker, Christopher C., Meek, Garrett A., Fobe, Theodore L., and Shirts, Michael R. Wed . "Using a Coarse-Grained Modeling Framework to Identify Oligomeric Motifs with Tunable Secondary Structure". United States. https://doi.org/10.1021/acs.jctc.1c00528. https://www.osti.gov/servlets/purl/1899344.
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@article{osti_1899344,
title = {Using a Coarse-Grained Modeling Framework to Identify Oligomeric Motifs with Tunable Secondary Structure},
author = {Walker, Christopher C. and Meek, Garrett A. and Fobe, Theodore L. and Shirts, Michael R.},
abstractNote = {Coarse-grained modeling can be used to explore general theories that are independent of specific chemical detail. In this paper, we present cg_openmm, a Python-based simulation framework for modeling coarse-grained hetero-oligomers and screening them for structural and thermodynamic characteristics of cooperative secondary structures. cg_openmm facilitates the building of coarse-grained topology and random starting configurations, setup of GPU-accelerated replica exchange molecular dynamics simulations with the OpenMM software package, and features a suite of postprocessing thermodynamic and structural analysis tools. In particular, native contact analysis, heat capacity calculations, and free energy of folding calculations are used to identify and characterize cooperative folding transitions and stable secondary structures. In this work, we demonstrate the capabilities of cg_openmm on a simple 1–1 Lennard-Jones coarse-grained model, in which each residue contains 1 backbone and 1 side-chain bead. By scanning both nonbonded and bonded force-field parameter spaces at the coarse-grained level, we identify and characterize sets of parameters which result in the formation of stable helices through cooperative folding transitions. Furthermore, we show that the geometries and stabilities of these helices can be tuned by manipulating the force-field parameters.},
doi = {10.1021/acs.jctc.1c00528},
journal = {Journal of Chemical Theory and Computation},
number = 10,
volume = 17,
place = {United States},
year = {Wed Sep 08 00:00:00 EDT 2021},
month = {Wed Sep 08 00:00:00 EDT 2021}
}
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https://doi.org/10.1021/acs.jctc.1c00528
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