(770c) Atomistic and Coarse-Grained Molecular Dynamics Simulations of Elastin-like Peptides and Collagen-like Peptides

In this talk we will present our atomistic and coarse-grained molecular dynamics (MD) simulation studies of thermoresponsive polypeptides, specifically elastin-like peptides (ELP) and collagen-like peptides (CLP). ELPs are polypeptides that mimic the extracellular matrix protein, elastin, and are composed of repeat units of (VPGXG), where V, P, and G, and valine, proline, and glycine, respectively. The fourth residue, X, is termed the guest residue and can be any amino acid besides proline. Aqueous solutions of ELPs undergo a lower critical solution temperature (LCST)-like phase transition, which means ELPs are soluble below the transition temperature, T_t, and insoluble above T_t. The T_t of ELPs can be tuned via conjugation to other thermoresponsive biomolecules such as CLPs and by varying the identity of the guest residue, X. We use all-atom (AA) and coarse-grained (CG) simulations to elucidate how the choice of the guest residue in each pentad and the number of pentads impact the LCST-like transition of ELP and ELP-CLP conjugates. While AA simulations provide detailed analysis of water arrangement around the ELPs (hydration analysis) and propensity for beta-turns, they are restricted to a few ELP chains. So we use the structural data from AA simulations to inform our ELP CG model to capture the atomistically-informed stiffness and propensity for secondary structure. These implicit solvent CG models then enable simulations at experimentally relevant length and time scales. Using the hydration analysis and the data on propensity to form secondary structures obtained from AA simulations and the trends in ELP aggregation from CG simulations, we are able to explain the experimental observations in T_t of ELP and ELP-CLP conjugates with W and F as the guest residues. We also show that in addition to the choice of W vs. F guest residues, their relative amounts – i.e. the ratio of F to W – in the ELP sequence, and the length of the ELP sequence affect the T_t of ELP and ELP-CLP conjugates.