Biology subjects

Barrat, J.-L.

Publications and source records attributed to Barrat, J.-L..

3 recordsLinked to original sources

bioRxiv2024

Intrinsically disordered proteins can behave as different polymers across their conformational ensemble

Intrinsically disordered proteins (IDPs) are macromolecules, which in contrast to well-folded proteins, explore a large number of conformationally heterogeneous states. In this work, we investigate the conformational space of the disordered protein {beta}-casein using Hamiltonian replica exchange atomistic molecular dynamics simulations in explicit water. The energy landscape contains a global minimum along with two shallow funnels. Employing static polymeric scaling laws separately for individual funnels, we find that they cannot be described by the same polymeric scaling exponent. Around the global minimum, the conformations are globular, whereas in the vicinity of local minima we recover coil-like scaling. To elucidate the implications of structural diversity on equilibrium dynamics, we initiate standard molecular dynamics simulations in the NVT ensemble with representative conformations from each funnel. Global and internal motions for different classes of trajectories show heterogeneous dynamics with globule to coil-like signatures. Thus, IDPs can behave as entirely different polymers in different regions of the conformational space. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/615433v2_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@14a0ddorg.highwire.dtl.DTLVardef@4d2af5org.highwire.dtl.DTLVardef@3f4b64org.highwire.dtl.DTLVardef@16ea7e7_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2023

Sequence length controls coil-to-globule transition in elastin-like polypeptides

Phase separation of disordered proteins resulting in the formation of biocondensates has received significant attention due to its fundamental role in cellular organization and functioning and is sought after in many applications. For instance, the liquid-liquid phase separation of tropoelastin initiates the hierarchical assembly process of elastic fibers, which are key components of the extracellular matrix providing resilience and elasticity to biological tissues. Inspired by the hydrophobic domains of tropoelastin, elastin-like polypeptides (ELPs) were derived which exhibit a similar phase behavior. Even though, it appeared almost certain that elastin condensates retain liquid-like properties, a recent experimental study questioned this viewpoint by demonstrating that the aggregate state of elastin-derived materials can depend on the length of hydrophobic domains. Here, we employ state-of-the-art atomistic modeling to resolve the conformational ensembles of a single ELP as a function of its sequence length in the temperature range relevant to possible applications. For the first time, we report the free energy profiles of ELPs in the vicinity of conformational transitions which show more compact polypeptide conformations at higher temperatures in accord with their thermoresponsive nature. We access the conformations visited by ELPs through descriptors from polymer physics. We find that short ELPs always remain in coil-like conformations, while the longer ones prefer globule states. The former engages in intrapeptide hydrogen bonds temporarily retaining their liquid-like properties while the latter forms long-lived (hundreds of nanoseconds) intra-peptide hydrogen bonds attributed to ordered secondary structure motifs such as {beta}-bridges and turns. Our work demonstrates the importance of the sequence length as a modulator of conformational properties at a single chain and possibly explains the change in aggregate state in elastin condensates.

biophysics↗

bioRxiv2022

Structural and Dynamical Properties of Elastin-Like Peptides near their Lower Critical Solution Temperature

Elastin-like peptides (ELPs) are artificially derived intrinsically disordered proteins (IDPs) mimicking the hydrophobic repeat unit in the protein elastin. ELPs are characterized by a lower critical solution temperature (LCST) in aqueous media. Here, we investigate the sequence GVG(VPGVG)3 over a wide range of temperatures (below, around, and above the LCST) and peptide concentrations employing all-atom molecular dynamics simulations, where we focus on the role of intra- and inter-peptide interactions. We begin by investigating the structural properties of a single peptide that demonstrates a hydrophobic collapse with temperature, albeit moderate, as the sequence length is short. We observe a change in the interaction between two peptides from repulsive to attractive with temperature by evaluating the potential of mean force, indicating an LCST-like behaviour. Next, we explore dynamical and structural properties of peptides in multi-chain systems. We report the formation of dynamical aggregates with coil-like conformation, in which Val central residues play an important role. Moreover, the lifetime of contacts between chains strongly depends on the temperature and can be described by a power-law decay that is consistent with the LCST-like behaviour. Finally, the peptide translational and internal motion are slowed down by an increase in the peptide concentration and temperature.

biophysics↗