Structural and dynamical properties of elastin-like peptides near lower critical solution temperature

T. I. MOROZOVA; N. A. GARCÍA; J.-L. BARRAT

Zurich

Workshop; Workshop: From disordered biomolecular complexes to biological coacervates; 2022

CECAM-ETHZ

Elastin-like peptides (ELPs) are artificial peptides derived from hydrophobic domains of elastin, a protein that provides elasticity to biological tissues such as lungs, ligaments. ELPs exhibit a lower critical solution temperature (LCST) transition, where ELPs are dispersed in solution below the LSCT, while undergoing chain collapse and aggregation at temperatures above the LCST. The transition temperature does not only depend on the peptide properties — sequence and chain length — but also on solution properties, e.g., pH and salt concentration. All these stimuli-responsive features make ELPs promising candidates for biological applications from drug delivery to molecular switches. Moreover, ELPs are models for intrinsically disordered proteins that carry out many biologically important functions including cell signalling. Hence, the study of structural and dynamical properties of ELPs over a wide range of temperatures (below and above LCST) is of key interest. Here, we study the hydrophobic collapse and assembly of Gly-Val-Gly(-Val-Pro-Gly-Val-Gly)3 employing Molecular Dynamics simulation with an atomistic resolution. We investigate the phase behaviour and dynamics as a function of peptide concentration and temperature. In multi-peptide simulations, we identify the amino acids which are more likely to drive the aggregation. Furthermore, our numerical study is complemented with neutron scattering experiments carried out by our collaborators at Institut Laue–Langevin.