Coarse-Graining Peptide Chains – from Particles to Fields
Prof. Dr. Michele Cascella (Chemistry Department, University of Oslo)

I will present a new model of peptide chains based on the hybrid particle field approach [1]. The intramolecular potential is built on a two-bead coarse grain mapping for each amino acid. A combined potential for the bending and the torsional degrees of freedom ensures the stabilisation of secondary structure elements in the conformational space of the polypeptide. The electrostatic dipoles associated with the peptide bonds of the main chain are reconstructed by a topological procedure following previous works [2-3] The intermolecular interactions comprising both the solute and the explicit solvent are treated by a density functional-based mean-field potential.
Molecular dynamics simulations on a series of test systems show how the model is able to capture all the main features of polypeptides. In particular, homopolymers of different lengths yield a complex folding phase diagram, covering from the collapsed to swollen state. Moreover, simulations on models of a four-helix bundle and of an alpha+beta peptide evidence how the collapse of the hydrophobic core drives the appearance of both folded motifs and the stabilization of tertiary or quaternary assemblies. Finally, the polypeptide model is able to structurally respond to the environmental changes caused by the presence of a lipid bilayer.

References

[1] S. L. Bore, G. Milano, and M. Cascella J. Chem. Theory Comput 2018, 14, 1120–1130.

[2] M. Cascella et al. J. Chem. Theory Comput. 2008, 4, 1378–1385.

[3]D. Alemani et al. J. Chem. Theory Comput. 2010, 6, 315–324.