Folding Coarse-Grained Oligomer Models with PyRosetta

Fobe, Theodore L.; Walker, Christopher C.; Meek, Garrett A.; Shirts, Michael R.

doi:10.1021/acs.jctc.2c00519

Title: Folding Coarse-Grained Oligomer Models with PyRosetta

Journal Article · Fri Sep 30 00:00:00 EDT 2022 · Journal of Chemical Theory and Computation

DOI:https://doi.org/10.1021/acs.jctc.2c00519· OSTI ID:1899349

^[1];

^[1]; Meek, Garrett A. ^[1];

^[1]

Univ. of Colorado, Boulder, CO (United States)

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.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Univ. of Colorado, Boulder, CO (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Materials Sciences & Engineering Division; National Science Foundation (NSF)

Grant/Contract Number:: SC0018651; ACI-1548562

OSTI ID:: 1899349

Journal Information:: Journal of Chemical Theory and Computation, Vol. 18, Issue 10; Related Information: https://github.com/shirtsgroup/cg_pyrosetta; ISSN 1549-9618

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

References (69)

A Field Guide to Foldamers Hill, David J.; Mio, Matthew J.; Prince, Ryan B. Chemical Reviews, Vol. 101, Issue 12 https://doi.org/10.1021/cr990120t	journal	December 2001
Foldamers: A Manifesto Gellman, Samuel H. Accounts of Chemical Research, Vol. 31, Issue 4 https://doi.org/10.1021/ar960298r	journal	April 1998
Therapeutic Potential of Foldamers: From Chemical Biology Tools To Drug Candidates? Gopalakrishnan, Ranganath; Frolov, Andrey I.; Knerr, Laurent Journal of Medicinal Chemistry, Vol. 59, Issue 21 https://doi.org/10.1021/acs.jmedchem.6b00376	journal	July 2016
De novo design and in vivo activity of conformationally restrained antimicrobial arylamide foldamers Choi, Sungwook; Isaacs, Andre; Clements, Dylan Proceedings of the National Academy of Sciences, Vol. 106, Issue 17 https://doi.org/10.1073/pnas.0811818106	journal	April 2009
De Novo Design of Antimicrobial Polymers, Foldamers, and Small Molecules: From Discovery to Practical Applications Tew, Gregory N.; Scott, Richard W.; Klein, Michael L. Accounts of Chemical Research, Vol. 43, Issue 1 https://doi.org/10.1021/ar900036b	journal	January 2010
A Rationally Designed Aldolase Foldamer Müller, Manuel M.; Windsor, Matthew A.; Pomerantz, William C. Angewandte Chemie International Edition, Vol. 48, Issue 5 https://doi.org/10.1002/anie.200804996	journal	January 2009
Folded biomimetic oligomers for enantioselective catalysis Maayan, G.; Ward, M. D.; Kirshenbaum, K. Proceedings of the National Academy of Sciences, Vol. 106, Issue 33 https://doi.org/10.1073/pnas.0903187106	journal	August 2009
Foldamer-Based Molecular Recognition Prince, Ryan B.; Barnes, Stephanie A.; Moore, Jeffrey S. Journal of the American Chemical Society, Vol. 122, Issue 12 https://doi.org/10.1021/ja993830p	journal	March 2000
Biomimetic Nanostructures: Creating a High-Affinity Zinc-Binding Site in a Folded Nonbiological Polymer Lee, Byoung-Chul; Chu, Tammy K.; Dill, Ken A. Journal of the American Chemical Society, Vol. 130, Issue 27 https://doi.org/10.1021/ja802125x	journal	July 2008
Free-floating ultrathin two-dimensional crystals from sequence-specific peptoid polymers Nam, Ki Tae; Shelby, Sarah A.; Choi, Philip H. Nature Materials, Vol. 9, Issue 5 https://doi.org/10.1038/nmat2742	journal	April 2010
β-Peptides: From Structure to Function Cheng, Richard P.; Gellman, Samuel H.; DeGrado, William F. Chemical Reviews, Vol. 101, Issue 10 https://doi.org/10.1021/cr000045i	journal	October 2001
Helices and other secondary structures of β- and γ-peptides Seebach, Dieter; Hook, David F.; Glättli, Alice Biopolymers, Vol. 84, Issue 1 https://doi.org/10.1002/bip.20391	journal	January 2006
A Peptoid Square Helix via Synergistic Control of Backbone Dihedral Angles Gorske, Benjamin C.; Mumford, Emily M.; Gerrity, Charles G. Journal of the American Chemical Society, Vol. 139, Issue 24 https://doi.org/10.1021/jacs.7b02319	journal	June 2017
Toward the Synthesis of Artificial Proteins Burkoth, Timothy S.; Beausoleil, Eric; Kaur, Surinder Chemistry & Biology, Vol. 9, Issue 5 https://doi.org/10.1016/s1074-5521(02)00140-0	journal	May 2002
Oligooxopiperazines as Nonpeptidic α-Helix Mimetics Tošovská, Petra; Arora, Paramjit S. Organic Letters, Vol. 12, Issue 7 https://doi.org/10.1021/ol1003143	journal	March 2010
A γ-Amino Acid That Favors 12/10-Helical Secondary Structure in α/γ-Peptides Giuliano, Michael W.; Maynard, Stacy J.; Almeida, Aaron M. Journal of the American Chemical Society, Vol. 136, Issue 42 https://doi.org/10.1021/ja5076585	journal	October 2014
Impact of γ-Amino Acid Residue Preorganization on α/γ-Peptide Foldamer Helicity in Aqueous Solution Fisher, Brian F.; Gellman, Samuel H. Journal of the American Chemical Society, Vol. 138, Issue 34 https://doi.org/10.1021/jacs.6b06177	journal	August 2016
Metal-Coordination-Assisted Folding and Guest Binding in Helical Aromatic Oligoamide Molecular Capsules Horeau, Maxime; Lautrette, Guillaume; Wicher, Barbara Angewandte Chemie International Edition, Vol. 56, Issue 24 https://doi.org/10.1002/anie.201701693	journal	May 2017
Single helically folded aromatic oligoamides that mimic the charge surface of double-stranded B-DNA Ziach, Krzysztof; Chollet, Céline; Parissi, Vincent Nature Chemistry, Vol. 10, Issue 5 https://doi.org/10.1038/s41557-018-0018-7	journal	April 2018
Non-haemolytic β-amino-acid oligomers Porter, Emilie A.; Wang, Xifang; Lee, Hee-Seung Nature, Vol. 404, Issue 6778 https://doi.org/10.1038/35007145	journal	April 2000
Designing Helical Molecular Capsules Based on Folded Aromatic Amide Oligomers Ferrand, Yann; Huc, Ivan Accounts of Chemical Research, Vol. 51, Issue 4 https://doi.org/10.1021/acs.accounts.8b00075	journal	March 2018
Molecular Recognition within the Cavity of a Foldamer Helix Bundle: Encapsulation of Primary Alcohols in Aqueous Conditions Collie, Gavin W.; Bailly, Remy; Pulka-Ziach, Karolina Journal of the American Chemical Society, Vol. 139, Issue 17 https://doi.org/10.1021/jacs.7b00181	journal	March 2017
Solid Phase Synthesis of Aromatic Oligoamides: Application to Helical Water-Soluble Foldamers Baptiste, Benoît; Douat-Casassus, Céline; Laxmi-Reddy, Katta The Journal of Organic Chemistry, Vol. 75, Issue 21 https://doi.org/10.1021/jo101360h	journal	October 2010
Improving Foldamer Synthesis through Protecting Group Induced Unfolding of Aromatic Oligoamides Zhang, Aimin; Ferguson, Joseph S.; Yamato, Kazuhiro Organic Letters, Vol. 8, Issue 22 https://doi.org/10.1021/ol062103d	journal	October 2006
Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism Francis, Andrew J.; Resendiz, Marino J. E. Journal of Visualized Experiments, Issue 125 https://doi.org/10.3791/56189	journal	July 2017
Rosetta3: An Object-Oriented Software Suite for the Simulation and Design of Macromolecules Leaver-Fay, Andrew; Tyka, Michael; Lewis, Steven M. Computer Methods, Part C https://doi.org/10.1016/B978-0-12-381270-4.00019-6	book	January 2011
Assembly of protein tertiary structures from fragments with similar local sequences using simulated annealing and bayesian scoring functions Simons, Kim T.; Kooperberg, Charles; Huang, Enoch Journal of Molecular Biology, Vol. 268, Issue 1 https://doi.org/10.1006/jmbi.1997.0959	journal	April 1997
Enhancing fragment-based protein structure prediction by customising fragment cardinality according to local secondary structure Abbass, Jad; Nebel, Jean-Christophe BMC Bioinformatics, Vol. 21, Issue 1 https://doi.org/10.1186/s12859-020-3491-0	journal	May 2020
A Smoothed Backbone-Dependent Rotamer Library for Proteins Derived from Adaptive Kernel Density Estimates and Regressions Shapovalov, Maxim V.; Dunbrack, Roland L. Structure, Vol. 19, Issue 6 https://doi.org/10.1016/j.str.2011.03.019	journal	June 2011
Homology modeling using parametric alignment ensemble generation with consensus and energy-based model selection Chivian, Dylan; Baker, David Nucleic Acids Research, Vol. 34, Issue 17 https://doi.org/10.1093/nar/gkl480	journal	August 2006
Structure prediction for CASP8 with all-atom refinement using Rosetta Raman, Srivatsan; Vernon, Robert; Thompson, James Proteins: Structure, Function, and Bioinformatics, Vol. 77, Issue S9 https://doi.org/10.1002/prot.22540	journal	January 2009
The Rosetta All-Atom Energy Function for Macromolecular Modeling and Design Alford, Rebecca F.; Leaver-Fay, Andrew; Jeliazkov, Jeliazko R. Journal of Chemical Theory and Computation, Vol. 13, Issue 6 https://doi.org/10.1021/acs.jctc.7b00125	journal	May 2017
Improved protein structure refinement guided by deep learning based accuracy estimation Hiranuma, Naozumi; Park, Hahnbeom; Baek, Minkyung Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-21511-x	journal	February 2021
Deep learning 3D structures Singh, Arunima Nature Methods, Vol. 17, Issue 3 https://doi.org/10.1038/s41592-020-0779-y	journal	March 2020
Protein Structure Prediction Using Rosetta Rohl, Carol A.; Strauss, Charlie E. M.; Misura, Kira M. S. Methods in Enzymology https://doi.org/10.1016/S0076-6879(04)83004-0	book	January 2004
FoldamerDB: a database of peptidic foldamers Nizami, Bilal; Bereczki-Szakál, Dorottya; Varró, Nikolett Nucleic Acids Research https://doi.org/10.1093/nar/gkz993	journal	November 2019
Helical arylamide foldamers: structure prediction by molecular dynamics simulations Liu, Zhiwei; Abramyan, Ara M.; Pophristic, Vojislava New Journal of Chemistry, Vol. 39, Issue 5 https://doi.org/10.1039/c4nj01925c	journal	January 2015
Foldamer dynamics expressed via Markov state models. I. Explicit solvent molecular-dynamics simulations in acetonitrile, chloroform, methanol, and water Elmer, Sidney P.; Park, Sanghyun; Pande, Vijay S. The Journal of Chemical Physics, Vol. 123, Issue 11 https://doi.org/10.1063/1.2001648	journal	September 2005
De novo structure prediction and experimental characterization of folded peptoid oligomers Butterfoss, G. L.; Yoo, B.; Jaworski, J. N. Proceedings of the National Academy of Sciences, Vol. 109, Issue 36 https://doi.org/10.1073/pnas.1209945109	journal	August 2012
Peptoid conformational free energy landscapes from implicit-solvent molecular simulations in AMBER Voelz, Vincent A.; Dill, Ken A.; Chorny, Ilya Biopolymers, Vol. 96, Issue 5 https://doi.org/10.1002/bip.21575	journal	December 2010
Evaluating the Conformations and Dynamics of Peptoid Macrocycles Eastwood, James R. B.; Jiang, Linhai; Bonneau, Richard The Journal of Physical Chemistry B, Vol. 126, Issue 28 https://doi.org/10.1021/acs.jpcb.2c01669	journal	July 2022
Predicting Order and Disorder for β-Peptide Foldamers in Water Németh, Lukács J.; Hegedüs, Zsófia; Martinek, Tamás A. Journal of Chemical Information and Modeling, Vol. 54, Issue 10 https://doi.org/10.1021/ci5003476	journal	September 2014
Zipper-Featured δ-Peptide Foldamers Driven by Donor−Acceptor Interaction. Design, Synthesis, and Characterization Zhao, Xin; Jia, Mu-Xin; Jiang, Xi-Kui The Journal of Organic Chemistry, Vol. 69, Issue 2 https://doi.org/10.1021/jo035149i	journal	December 2003
Foldamer Architectures of Triazine-Based Sequence-Defined Polymers Investigated with Molecular Dynamics Simulations and Enhanced Sampling Methods Ahn, Surl-Hee; Grate, Jay W. The Journal of Physical Chemistry B, Vol. 123, Issue 44 https://doi.org/10.1021/acs.jpcb.9b06067	journal	October 2019
Interplay of secondary and tertiary folding in abiotic foldamers Mazzier, Daniela; De, Soumen; Wicher, Barbara Chemical Science, Vol. 10, Issue 29 https://doi.org/10.1039/c9sc01322a	journal	January 2019
Derivation of coarse-grained potentials via multistate iterative Boltzmann inversion Moore, Timothy C.; Iacovella, Christopher R.; McCabe, Clare The Journal of Chemical Physics, Vol. 140, Issue 22 https://doi.org/10.1063/1.4880555	journal	June 2014
Dynamic force matching: A method for constructing dynamical coarse-grained models with realistic time dependence Davtyan, Aram; Dama, James F.; Voth, Gregory A. The Journal of Chemical Physics, Vol. 142, Issue 15 https://doi.org/10.1063/1.4917454	journal	April 2015
Protein modeling and structure prediction with a reduced representation. Kolinski, Andrzej Acta Biochimica Polonica, Vol. 51, Issue 2 https://doi.org/10.18388/abp.2004_3575	journal	June 2004
Perspective: Coarse-grained models for biomolecular systems Noid, W. G. The Journal of Chemical Physics, Vol. 139, Issue 9 https://doi.org/10.1063/1.4818908	journal	September 2013
Toy amphiphiles on the computer: What can we learn from generic models? Schmid, Friederike Macromolecular Rapid Communications, Vol. 30, Issue 9-10 https://doi.org/10.1002/marc.200800750	journal	May 2009
A lattice statistical mechanics model of the conformational and sequence spaces of proteins Lau, Kit Fun; Dill, Ken A. Macromolecules, Vol. 22, Issue 10 https://doi.org/10.1021/ma00200a030	journal	October 1989
A test of lattice protein folding algorithms. Yue, K.; Fiebig, K. M.; Thomas, P. D. Proceedings of the National Academy of Sciences, Vol. 92, Issue 1 https://doi.org/10.1073/pnas.92.1.325	journal	January 1995
Practically Useful: What the R osetta Protein Modeling Suite Can Do for You Kaufmann, Kristian W.; Lemmon, Gordon H.; DeLuca, Samuel L. Biochemistry, Vol. 49, Issue 14 https://doi.org/10.1021/bi902153g	journal	April 2010
PyRosetta: a script-based interface for implementing molecular modeling algorithms using Rosetta Chaudhury, S.; Lyskov, S.; Gray, J. J. Bioinformatics, Vol. 26, Issue 5, p. 689-691 https://doi.org/10.1093/bioinformatics/btq007	journal	January 2010
Computer simulation of protein folding Levitt, Michael; Warshel, Arieh Nature, Vol. 253, Issue 5494 https://doi.org/10.1038/253694a0	journal	February 1975
The MARTINI Force Field: Coarse Grained Model for Biomolecular Simulations Marrink, Siewert J.; Risselada, H. Jelger; Yefimov, Serge The Journal of Physical Chemistry B, Vol. 111, Issue 27 https://doi.org/10.1021/jp071097f	journal	July 2007
A backbone-based theory of protein folding Rose, G. D.; Fleming, P. J.; Banavar, J. R. Proceedings of the National Academy of Sciences, Vol. 103, Issue 45 https://doi.org/10.1073/pnas.0606843103	journal	October 2006
Simple data and workflow management with the signac framework Adorf, Carl S.; Dodd, Paul M.; Ramasubramani, Vyas Computational Materials Science, Vol. 146 https://doi.org/10.1016/j.commatsci.2018.01.035	journal	April 2018
Monte Carlo-minimization approach to the multiple-minima problem in protein folding. Li, Z.; Scheraga, H. A. Proceedings of the National Academy of Sciences, Vol. 84, Issue 19 https://doi.org/10.1073/pnas.84.19.6611	journal	October 1987
Global Optimization by Basin-Hopping and the Lowest Energy Structures of Lennard-Jones Clusters Containing up to 110 Atoms Wales, David J.; Doye, Jonathan P. K. The Journal of Physical Chemistry A, Vol. 101, Issue 28 https://doi.org/10.1021/jp970984n	journal	July 1997
Clustering Molecular Dynamics Trajectories: 1. Characterizing the Performance of Different Clustering Algorithms Shao, Jianyin; Tanner, Stephen W.; Thompson, Nephi Journal of Chemical Theory and Computation, Vol. 3, Issue 6 https://doi.org/10.1021/ct700119m	journal	October 2007
MDTraj: A Modern Open Library for the Analysis of Molecular Dynamics Trajectories McGibbon, Robert T.; Beauchamp, Kyle A.; Harrigan, Matthew P. Biophysical Journal, Vol. 109, Issue 8 https://doi.org/10.1016/j.bpj.2015.08.015	journal	October 2015
DBSCAN Revisited, Revisited: Why and How You Should (Still) Use DBSCAN Schubert, Erich; Sander, Jörg; Ester, Martin ACM Transactions on Database Systems, Vol. 42, Issue 3 https://doi.org/10.1145/3068335	journal	August 2017
Density-based cluster algorithms for the identification of core sets Lemke, Oliver; Keller, Bettina G. The Journal of Chemical Physics, Vol. 145, Issue 16 https://doi.org/10.1063/1.4965440	journal	October 2016
Using a Coarse-Grained Modeling Framework to Identify Oligomeric Motifs with Tunable Secondary Structure Walker, Christopher C.; Meek, Garrett A.; Fobe, Theodore L. Journal of Chemical Theory and Computation, Vol. 17, Issue 10 https://doi.org/10.1021/acs.jctc.1c00528	journal	September 2021
Identifying ligand binding sites and poses using GPU-accelerated Hamiltonian replica exchange molecular dynamics Wang, Kai; Chodera, John D.; Yang, Yanzhi Journal of Computer-Aided Molecular Design, Vol. 27, Issue 12 https://doi.org/10.1007/s10822-013-9689-8	journal	December 2013
SPICKER: A clustering approach to identify near-native protein folds Zhang, Yang; Skolnick, Jeffrey Journal of Computational Chemistry, Vol. 25, Issue 6 https://doi.org/10.1002/jcc.20011	journal	January 2004
SciPy 1.0: fundamental algorithms for scientific computing in Python Virtanen, Pauli; Gommers, Ralf; Oliphant, Travis E. Nature Methods https://doi.org/10.1038/s41592-019-0686-2	journal	February 2020
Silhouettes: A graphical aid to the interpretation and validation of cluster analysis Rousseeuw, Peter J. Journal of Computational and Applied Mathematics, Vol. 20 https://doi.org/10.1016/0377-0427(87)90125-7	journal	November 1987

Similar Records

How Cooperatively Folding Are Homopolymer Molecular Knots?

Journal Article · Thu Sep 22 00:00:00 EDT 2022 · Macromolecules · OSTI ID:1899349

Walker, Christopher C.; Fobe, Theodore L.; Shirts, Michael R.

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

Journal Article · Wed Sep 08 00:00:00 EDT 2021 · Journal of Chemical Theory and Computation · OSTI ID:1899349

Walker, Christopher C.; Meek, Garrett A.; Fobe, Theodore L.; +1 more

The Dynameomics Entropy Dictionary: A Large-Scale Assessment of Conformational Entropy across Protein Fold Space

Journal Article · Tue Apr 04 00:00:00 EDT 2017 · Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry · OSTI ID:1899349

Towse, Clare-Louise; Akke, Mikael; Daggett, Valerie

Related Subjects

36 MATERIALS SCIENCE
Rosetta
foldamers
computational molecular design
chemical structure
cluster chemistry
cluster structure
energy

Title: Folding Coarse-Grained Oligomer Models with PyRosetta

Citation Formats

References (69)

Similar Records

Related Subjects