Folding Coarse-Grained Oligomer Models with PyRosetta
Abstract
Non-biological foldamers are a promising class of macromolecules that share similarities to classical biopolymers such as proteins and nucleic acids. Currently, designing novel foldamers is a non-trivial process, often involving many iterations of trial synthesis and characterization until folded structures are observed. In this work, we aim to tackle these foldamer design challenges using computational modeling techniques. We developed CG PyRosetta, an extension to the popular protein folding python package, PyRosetta, which introduces coarse-grained (CG) residues into PyRosetta, enabling the folding of toy CG foldamer models. Although these models are simplified, they can help explore overarching physical hypotheses about how oligomers can form. Through systematic variation of CG parameters in these models, we can investigate various folding hypotheses at the CG scale to inform the design process of new foldamer chemistries. In this study, we demonstrate CG PyRosetta’s ability to identify minimum energy structures with a diverse structural search over a range of simple models, as well as two hypothesis-driven parameter scans investigating the effects of side-chain size and internal backbone angle on secondary structures. We are able to identify several types of secondary structures from single- and double-helices to sheet-like and knot-like structures. Here, we show how side-chain sizemore »
- Publication Date:
- Research Org.:
- Univ. of Colorado, Boulder, CO (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES). Materials Sciences & Engineering Division; National Science Foundation (NSF)
- OSTI Identifier:
- 1899349
- Grant/Contract Number:
- SC0018651; ACI-1548562
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Chemical Theory and Computation
- Additional Journal Information:
- Journal Volume: 18; Journal Issue: 10; Related Information: https://github.com/shirtsgroup/cg_pyrosetta; Journal ID: ISSN 1549-9618
- Publisher:
- American Chemical Society
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 36 MATERIALS SCIENCE; Rosetta; foldamers; computational molecular design; chemical structure; cluster chemistry; cluster structure; energy
Citation Formats
Fobe, Theodore L., Walker, Christopher C., Meek, Garrett A., and Shirts, Michael R. Folding Coarse-Grained Oligomer Models with PyRosetta. United States: N. p., 2022.
Web. doi:10.1021/acs.jctc.2c00519.
Fobe, Theodore L., Walker, Christopher C., Meek, Garrett A., & Shirts, Michael R. Folding Coarse-Grained Oligomer Models with PyRosetta. United States. https://doi.org/10.1021/acs.jctc.2c00519
Fobe, Theodore L., Walker, Christopher C., Meek, Garrett A., and Shirts, Michael R. Fri .
"Folding Coarse-Grained Oligomer Models with PyRosetta". United States. https://doi.org/10.1021/acs.jctc.2c00519. https://www.osti.gov/servlets/purl/1899349.
@article{osti_1899349,
title = {Folding Coarse-Grained Oligomer Models with PyRosetta},
author = {Fobe, Theodore L. and Walker, Christopher C. and Meek, Garrett A. and Shirts, Michael R.},
abstractNote = {Non-biological foldamers are a promising class of macromolecules that share similarities to classical biopolymers such as proteins and nucleic acids. Currently, designing novel foldamers is a non-trivial process, often involving many iterations of trial synthesis and characterization until folded structures are observed. In this work, we aim to tackle these foldamer design challenges using computational modeling techniques. We developed CG PyRosetta, an extension to the popular protein folding python package, PyRosetta, which introduces coarse-grained (CG) residues into PyRosetta, enabling the folding of toy CG foldamer models. Although these models are simplified, they can help explore overarching physical hypotheses about how oligomers can form. Through systematic variation of CG parameters in these models, we can investigate various folding hypotheses at the CG scale to inform the design process of new foldamer chemistries. In this study, we demonstrate CG PyRosetta’s ability to identify minimum energy structures with a diverse structural search over a range of simple models, as well as two hypothesis-driven parameter scans investigating the effects of side-chain size and internal backbone angle on secondary structures. We are able to identify several types of secondary structures from single- and double-helices to sheet-like and knot-like structures. Here, we show how side-chain size and backbone bond angle both play an important role in the structure and energetics of these toy models. Optimal side-chain sizes promote favorable packing of side chains, while specific backbone bond angles influence the specific helix type found in folded structures.},
doi = {10.1021/acs.jctc.2c00519},
journal = {Journal of Chemical Theory and Computation},
number = 10,
volume = 18,
place = {United States},
year = {Fri Sep 30 00:00:00 EDT 2022},
month = {Fri Sep 30 00:00:00 EDT 2022}
}
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