Hydration dynamics protein fluctuations

Li TP, Hassanali AAP, Kao YT, Zhong DP, Singer SJ (2007) Hydration dynamics and time scales of coupled water-protein fluctuations. J Am Chem Soc 129(11) 3376-3382... 

Rosenberg, A. and Somogyi, B. (1986) Conformational fluctuations, thermal stability and hydration of proteins, studies by hydrogen exchange kinetics. n Dynamic of Biochemical systems, edited by S. Damjanovich, T.Keleti and L.Tron, pp. 101-112. Amsterdam Elsevier. 

HYDRATION DYNAMICS AND COUPLED WATER-PROTEIN FLUCTUATIONS PROBED BY INTRINSIC TRYPTOPHAN... 

We recently developed a systematic method that uses the intrinsic tryptophan residue (Trp or W) as a local optical probe [49, 50]. Using site-directed mutagenesis, tryptophan can be mutated into different positions one at a time to scan protein surfaces. With femtosecond temporal and single-residue spatial resolution, the fluorescence Stokes shift of the local excited Trp can be followed in real time, and thus, the location, dynamics, and functional roles of protein-water interactions can be studied directly. With MD simulations, the solvation by water and protein (residues) is differentiated carefully to determine the hydration dynamics. Here, we focus our own work and review our recent systematic studies on hydration dynamics and protein-water fluctuations in a series of biological systems using the powerful intrinsic tryptophan as a local optical probe, and thus reveal the dynamic role of hydrating water molecules around proteins, which is a longstanding unresolved problem and a topic central to protein science. 

Biomolecular recognition is mediated by water motions, and the dynamics of associated water directly determine local structural fluctuation of interacting partners [4, 9, 91]. The time scales of these interactions reflect their flexibility and adaptability. For water at protein surfaces, the studies of melittin and other proteins [45, 46] show water motions on tens of picoseconds. For trapped water in protein crevices or cavities, the dynamics becomes much slower and could extend to nanoseconds [40, 71, 92], These rigid water molecules are often hydrogen bonded to interior residues and become part of the structural integrity of many enzymes [92]. Here, we study local water motions in various environments, from a buried crevice to an exposed surface using site-selected tryptophan but with different protein conformations, to understand the correlation between hydration dynamics and conformational transitions and then relate them to biological function. 

MD simulations with either protein or water constrained at the instant of photoexcitation were performed for both isomer 1 and isomer 2. For isomer 1, because surface water relaxation dominates the slow component of the total Stokes shift, in Fig. 44a we show the result of simulations of isomer 1 with an ensemble of frozen protein configurations to examine the role of protein fluctuations. Clearly the long component of indole-water interactions disappears when the protein is constrained. This result shows that without protein fluctuations, indole-water relaxation over tens of picoseconds does not occur. Thus, although surface hydrating water molecules seem to drive the global solvation and, from the dynamics of the protein and water contributions, are apparently responsible for the slowest component of the solvation Stokes shift for isomer 1 (Fig. 42), local protein fluctuations are still required to facilitate this rearrangement process. When the protein is frozen, the ultrafast... 

The robust observation of surface hydration dynamics on two time scales and a series of correlations with protein properties provides a molecular picture of water motions and their coupling with protein fluctuations in the layer, as shown in Fig. 46. The dynamic exchange of hydration layer water with outside bulk... 

Figure 46. A unified molecular mechanism of protein hydration dynamics and coupled water-protein fluctuations. The initial ultrafast dynamics in a few picoseconds (ii) represents local collective orientation or small translation motions, which mainly depend on local electrostatic interactions. On the longer time (12), the water networks undergo structural rearrangements in the layer, which are strongly coupled with both protein fluctuations and bulk-water dynamic exchange.

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