Protein folding water dynamics

Compared to natively folded proteins, compact denatured states ( MGs ) experience a modest increase in the number of water molecules in the hydration layer, and a slightly smaller perturbation of hydration water dynamics. Soluble protein-water dynamical coupling has been elucidated by simultaneous examination of transitions in protein and water dynamics as a function of temperature. Hydrated proteins at room temperature exhibit liquid-like motion on the subnanosecond timescale and behave like glasses at low temperature. The dynamical (or glass) transition between the low-temperature glassy state and room-temperature liquid-like state plays an important role in energy flow processes in proteins (see Ref [86] and Chapters 7 and 11). 

Encouraging progress has been made recently, and we are now in an era of active application of molecular dynamics simulation to study the folding process. Because of the vital importance of water in protein folding and in the cell, the explicit repre-... 

In this section, we review our first examinations of tryptophan probing sensitivity and water dynamics in a series of important model systems from simple to complex, which range from a tripeptide [70], to a prototype membrane protein melittin [70], to a common drug transporter human serum albumin [71], and to lipid interface of a nanochannel [86]. At the end, we also give a special case that using indole moiety of tryptophan probes supramolecule crown ether solvation, and we observed solvent-induced supramolecule folding [87]. The obtained solvation dynamics in these systems are linked to properties or functions of these biological-relevant macromolecules. 

One of the major objectives of the physical chemistry studies in water and biomolecules is to fully reproduce the experimentally observed folding/ unfolding behavior of a typical model protein in water by means of molecular simulation. However, the all-atom molecular dynamics (MD) simulation of the folding of a protein from the fully unfolded state to the native structure remains computationally intractable when the size of the target protein is larger than 100 residues and when simulation is carried out with explicit water molecules (i.e., when complete, contextualized simulation is attempted) [1-3]. 

In protein crystal structures, ordered water molecules were frequently observed at instances where a-helices bend or fold. Molecular dynamic simu-... 

The dynamics of water around an extended, unfolded protein eertainly plays an important role in determining the rate of protein folding. For example, hydrophobic collapse involves movement of water molecules away from the region between two hydrophobic amino acid residues that form pair contact. Similarly, P bends (an important secondary structure of protein) also involve water mediation. In both of the examples, the water molecules in close proximity to the protein amino acids are expected to play a critical role through a subtle balance between enthalpic and entropic forces. 

The term lubricant of life was perhaps first used (in the sense being used here) by Barron et al. [24]. These authors observed by Raman spectroscopy fast dynamic events (in the picosecond timescale) where individual amino acid residues flicker between different secondary structure states. This flickering was attributed to fast dynamic events in bulk water and mediated through HBs of the amino acid residues with surrounding water molecules. These events driven by water could be the guiding force in many functions of proteins (folding and unfolding, enzyme kinetics, protein-DNA interaction), and hence water was termed the lubricant of life. 

As mentioned repeatedly, while we know a lot about the way in which proteins fold, comparatively little is known about the detailed role that water plays in these processes. The predominant interaction of water with proteins is through the formation of HBs. As discussed in previous chapters, the structure of the water surrounding a protein is continually changing, as HBs are broken and re-formed at a very rapid rate. This leads protein secondary structures such as alpha-helices and beta-sheets to inter-convert (or flicker ) among themselves on picosecond (10 s) timescales. It is the same dynamics that is reflected in SD at the protein surface. 

It is important to stress that the combination of both the low-Q QENS data and MD simulations allows us to understand on a molecular basis the onset of the reversible folding and the successive irreversible denaturation. In particular, by considering these results and the cited NMR and FTIR experimental data [15,19] it is possible to conclude that the denaturation of the protein and the dynamic crossover in its hydration water are causally related. In fact, all of their coincidences suggest that this high-r crossover could be a significant factor in the reversible denaturation process. We also note that the organization of water/biomolecules... 

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