Molecular Description of the LCST Behavior of an Elastin-Like Polypeptide

Abstract

Elastin-like polypeptides (ELPs) with the repeat sequence of VPGVG are widely used as a model system for investigation of lower critical solution temperature (LCST) transition behavior. In this paper, the effect of temperature on the structure, dynamics and association of (VPGVG) 18 in aqueous solution is investigated using atomistic molecular dynamics simulations. Our simulations show that as the temperature increases the ELP backbones undergo gradual conformational changes, which are attributed to the formation of more ordered secondary structures such as β-strands. In addition, increasing temperature changes the hydrophobicity of the ELP by exposure of hydrophobic valine-side chains to the solvent and hiding of proline residues. Based on our simulations, we conclude that the transition behavior of (VPGVG) 18 can be attributed to a combination of thermal disruption of the water network that surrounds the polypeptide, reduction of solvent accessible surface area of the polypeptide, and increase in its hydrophobicity. Simulations of the association of two (VPGVG) 18 molecules demonstrated that the observed gradual changes in the structural properties of the single polypeptide chain are enough to cause the aggregation of polypeptides above the LCST. These results lead us to propose that the LCST phase behavior of poly(VPGVG) is a collective phenomenon that originates from the correlated gradual changes in single polypeptide structure and the abrupt change in properties of hydration water around the peptide and is a result of a competition between peptide−peptide and peptide−water interactions. This is a computational study of an important intrinsically disordered peptide system that provides an atomic-level description of structural features and interactions that are relevant in the LCST phase behavior.

Self‐Assembly Toolbox of Tailored Supramolecular Architectures Based on an Amphiphilic Protein Library

“…This demonstrates that these arginine‐ and phenylalanine‐containing ELP molecules require a NaCl‐induced distinct trigger to collapse the amphiphilic ELP hydration shell and induce the classic LCST behavior described previously . Thus, our results confirm simulations of Li et al The LCST behavior observed here can be attributed to a combination of gradual transitions in single polypeptide structure as evidenced from CD spectroscopy and NaCl‐induced instant loss of hydration water around the polypeptide observed in turbidity measurements. The knowledge about the ELP solubility in different solvents and their molecular conformation and changes upon external stimuli such as temperature, salt, and pH is crucial for the development of new efficient and robust assembly protocols for desired SMPAs.…”

“…Based on results from Roberts et al and Dreher et al, it can be rationalized that even at room temperature (RT) the phenylalanine‐containing block domain is above T t and already holds an intrinsically ordered, presumably ß‐spiral, structure, whereas the hydrophilic part (e.g., arginine‐containing block), characterized with a much higher T t , exhibits a random coil at RT (Figure e). Regarding the structural and conformational changes of the amphiphilic ELP domains, our results confirm previous findings . The temperature‐dependent stepwise change of secondary structural elements can be attributed to gradual changes in single polypeptide substructures …”

“…Regarding the structural and conformational changes of the amphiphilic ELP domains, our results confirm previous findings . The temperature‐dependent stepwise change of secondary structural elements can be attributed to gradual changes in single polypeptide substructures …”

Self-Assembling VHH-Elastin-Like Peptides for Photodynamic Nanomedicine

“…11,12 ELPs reversibly transform from a soluble, disordered state below the transition temperature to an assembled state consisting of type-II β-turns, type-I β-turns, and β-strands above the transition temperature. 13−16 This behavior is thermodynamically driven: at the transition temperature, solvation of the protein backbone becomes entropically unfavorable. The conformational change and exposure of hydrophobic residues followed by assembly results in liberated water molecules, lowering the total energy of the system.…”

CAMELOT: A machine learning approach for coarse-grained simulations of aggregation of block-copolymeric protein sequences

“…The latter refer to regions that fail to fold into unique three-dimensional structures as autonomous units. [31][32][33][34] Accordingly, depending on their architecture, protein sequences that drive aggregation and phase separation may be classified as being intrinsically disordered or partially disordered block-copolymers (Figure 1). Molecular simulations can play a prominent role in uncovering the physical principles that govern the phase behavior of block-copolymeric proteins.…”