Theoretical and Computational Chemistry

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



We describe a process to build and simulate coarse-grained oligomers using temperature replica exchange molecular dynamics and analyze them for thermodynamic and structural characteristics of cooperative folding transitions. We also introduce a Python package (cg_openmm) to carry out these simulations and analyses. We demonstrate the capabilities of cg_openmm on a simple helix-forming homo-oligomer, systematically varying sets of force field parameters and studying the effects on folding cooperativity and helix stability. We find that small changes to force field parameters in the homo-oligomer model can dramatically affect cooperativity, stability, and even lead to helix-to-helix transitions. This software package enables large-scale screening of potential foldamer molecules and will be highly useful in the broader effort of understanding secondary structure formation in terms of non-chemically specific features of molecular models.


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Supplementary material

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cg openmm capability paper SI 5 27 21

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