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Register a new userCritical aspects of hierarchical protein folding
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We argue that the first order folding transitions of proteins observed at physiological chemical conditions end in a critical point for a given temperature and chemical potential of the surrounding water. We investigate this critical point using a hierarchical Hamiltonian and determine its universality class. This class differs qualitatively from those of other known models.
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Different aspects of protein folding are illustrated by simplified polymer models. Stressing the diversity of side chains (residues) leads one to view folding as the freezing transition of an heteropolymer. Technically, the most common approach to diversity is randomness, which is usually implemented in two body interactions (charges, polar character,..). On the other hand, the (almost) universal character of the protein backbone suggests that folding may also be viewed as the crystallization transition of an homopolymeric chain, the main ingredients of which are the peptide bond and chirality (proline and glycine notwithstanding). The model of a chiral dipolar chain leads to a unified picture of secondary structures, and to a possible connection of protein structures with ferroelectric domain theory.
Water plays a fundamental role in protein stability. However, the effect of the properties of water on the behaviour of proteins is only partially understood. Several theories have been proposed to give insight into the mechanisms of cold and pressure denaturation, or the limits of temperature and pressure above which no protein has a stable, functional state, or how unfolding and aggregation are related. Here we review our results based on a theoretical approach that can rationalise the water contribution to protein solutions free energy. We show, using Monte Carlo simulations, how we can rationalise experimental data with our recent results. We discuss how our findings can help develop new strategies for the design of novel synthetic biopolymers or possible approaches for mitigating neurodegenerative pathologies.
We develop a multi-scale approach to simulate hydrated nanobio systems under realistic condi- tions (e.g., nanoparticles and protein solutions at physiological conditions over time-scales up to hours). We combine atomistic simulations of water at bio-interfaces (e.g., proteins or membranes) and nano-interfaces (e.g., nanoparticles or graphene sheets) and coarse-grain models of hydration water for protein folding and protein design. We study protein self-assembly and crystallization, in bulk or under confinement, and the kinetics of protein adsorption onto nanoparticles, verify- ing our predictions in collaboration with several experimental groups. We try to find answers for fundamental questions (Why water is so important for life? Which properties make water unique for biological processes?) and applications (Can we design better drugs? Can we limit protein- aggregations causing Alzheimer? How to implement nanotheranostic?). Here we focus only on the two larger scales of our approach: (i) The coarse-grain description of hydrated proteins and protein folding at sub-nanometric length-scale and milliseconds-to-seconds time-scales, and (ii) the coarse-grain modeling of protein self-assembly on nanoparticles at 10-to-100 nm length-scale and seconds-to-hours time-scales.
A novel approach to protein folding dynamics is presented. We suggest that folding of protein may be mediated via interaction with solitons which propagate along the molecular chain. A simple toy model is presented in which a Sine-Gordon field interact with another field corresponding to the conformation angles of the protein. We demonstrate how a soliton carries this field over energy barriers and consequently enhances the rate of the folding process. The soliton compensate for its energy loss by pumping the energy gained by the folded field. This scenario does not change significantly even in the presence of dissipation and imposed disorder.
The problem of the helix-coil transition of biopolymers in explicit solvents, like water, with the ability for hydrogen bonding with solvent is addressed analytically using a suitably modified version of the Generalized Model of Polypeptide Chains. Besides the regular helix-coil transition, an additional coil-helix or reentrant transition is also found at lower temperatures. The reentrant transition arises due to competition between polymer-polymer and polymer-water hydrogen bonds. The balance between the two types of hydrogen bonding can be shifted to either direction through changes not only in temperature, but also by pressure, mechanical force, osmotic stress or other external influences. Both polypeptides and polynucleotides are considered within a unified formalism. Our approach provides an explanation of the experimental difficulty of observing the reentrant transition with pressure; and underscores the advantage of pulling experiments for studies of DNA. Results are discussed and compared with those reported in a number of recent publications with which a significant level of agreement is obtained.
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