How Cooperatively Folding Are Homopolymer Molecular Knots?

Journal Article · Thu Sep 22 00:00:00 EDT 2022 · Macromolecules

DOI:https://doi.org/10.1021/acs.macromol.2c00881· OSTI ID:1899348

Walker, Christopher C.  ^[1]; Fobe, Theodore L.  ^[1]; Shirts, Michael R.  ^[1]

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

Detailed thermodynamic analysis of complex systems with multiple stable configurational states allows for insight into the cooperativity of each individual transition. In this work, we derive a heat capacity decomposition comprising contributions from each individual configurational state, which together sum to a baseline heat capacity, and contributions from each state-to-state transition. We apply this analysis framework to a series of replica exchange molecular dynamics simulations of linear and 1-1 coarse-grained homo-oligomer models, which fold into stable, configurationally well-defined molecular knots, in order to better understand the parameters leading to stable and cooperative folding of these knots. We find that a stiff harmonic backbone bending angle potential is key to achieving knots with specific 3D structures. Tuning the backbone equilibrium angle in small increments yields a variety of knot topologies. Populations of different knotted states as a function of temperature can also be manipulated by tuning the backbone torsion stiffness or by adding side-chain beads. We find that sharp total heat capacity peaks for the homo-oligomer knots are largely due to a coil-to-globule transition rather than a cooperative knotting step. Furthermore, in some cases, the cooperativity of globule-to-knot and coil-to-globule transitions is comparable, suggesting that highly cooperative folding to knotted structures can be achieved by refining the model parameters or adding sequence specificity.

• Research Organization: Univ. of Colorado, Boulder, CO (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Science Foundation (NSF)
• Grant/Contract Number: SC0018651; ACI-1532235; ACI-1532236; ACI-1548562
• OSTI ID: 1899348
• Journal Information: Macromolecules, Vol. 55, Issue 19; Related Information: https://github.com/shirtsgroup/cg_openmm; ISSN 0024-9297
• Publisher: American Chemical Society
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
knots
foldamers
heat capacity
thermodynamics
chemical structure
mathematical methods
phase transitions
stiffness