Solvation of protein

S. Solvation. Difference in solvation of protein and ligand molecules in the complex and in isolation. 

Solvation of proteins in multicomponent systems is associated with interesting chemistry and has practical applications. Clever experiments have been carried out in this area, but there as yet has been no systematic exploration of the chemistry, such as is needed for development of a working picture of a protein in a multicomponent environment, particularly the complex environments of membranes, organelles, and cells. 

Since (NH4)2S04 requires much of the water available for the solvation of proteins, serum proteins may be fractionated on hydrophobic matrices. Doellgast and Plant (1976) chromatographed sera in the presence of 1 M (NH4)2S04 on L-phenylalanyl-Sepharose. IgA is desorbed by lowering the salt concentration to about 20% (800 mM). 

Clearly, the solvation Gibbs energy of proteins cannot be studied experimentally. This would require measurable vapor of the protein. Therefore, the only option of studying the solvation of proteins is by theoretical means. As we shall see below, in spite of the enormous complexity of the problem, theory does suggest some guidance as to how to dissect the problem into relatively small and manageable problems. 

Anton, M., D. W. Bolen and J. Rosgen. 2008. Structural thermodynamics of protein preferential solvation Osmolyte solvation of proteins, aminoacids, and peptides. Proteins Structure, Function, and Bioinformatics. 73, 802. 

Relation (6.17.17) is useful for a solute for which the solvation Gibbs energy can be determined. If we are interested in proteins as solutes, then (6.17.17) is impractical. However, we can still measure the solvation free energy of 5 in / relative to, say, pure A (e.g., solvation of protein in a solution relative to the solvation in pure water). The relevant relation is... 

H. Hansen-Goos, R. Roth, K. Mecke, and S. Dietrich, Solvation of proteins linking thermodynamics to geometry, Phys. Rev. Lett, 99, 128101 [2007]. 

Grebner C, Engels B (2012) A new tabu-search-based algorithm for solvation of proteins (in preparation)... 

Similar FEP/QM combinational calculations were performed to study tautomerism " and relative basic-ities/acidities in solution. Other applications of free energy simulation methods in solution include the study of the conformational equilibria of sugars " and determination of the solvation of protein cavities. Accurate determination of absolute or relative solvation free energies of simple molecules in a solvent has become an essential test for any new force field or free energy calculation method. 

Homoelle B J, Edington M D, Diffey W M and Beck W F 1998 Stimulated photon-echo and transientgrating studies of protein-matrix solvation dynamics and interexciton-state radiationless decay in a phycocyanin and allophycocyanin J. Phys. Chem. B 102 3044-52... 

Abstract. Molecular dynamics (MD) simulations of proteins provide descriptions of atomic motions, which allow to relate observable properties of proteins to microscopic processes. Unfortunately, such MD simulations require an enormous amount of computer time and, therefore, are limited to time scales of nanoseconds. We describe first a fast multiple time step structure adapted multipole method (FA-MUSAMM) to speed up the evaluation of the computationally most demanding Coulomb interactions in solvated protein models, secondly an application of this method aiming at a microscopic understanding of single molecule atomic force microscopy experiments, and, thirdly, a new method to predict slow conformational motions at microsecond time scales. 

Since f is a measurable quantity for, say, a protein, and since the latter can be considered to fail into category (3) in general, the friction factor provides some information regarding the eilipticity and/or solvation of the molecule. In the following discussion we attach the subscript 0 to both the friction factor and the associated radius of a nonsolvated spherical particle and use f and R without subscripts to signify these quantities in the general case. Because of Stokes law, we write... 

Protein molecules extracted from Escherichia coli ribosomes were examined by viscosity, sedimentation, and diffusion experiments for characterization with respect to molecular weight, hydration, and ellipticity. These dataf are examined in this and the following problem. Use Fig. 9.4a to estimate the axial ratio of the molecules, assuming a solvation of 0.26 g water (g protein)"V At 20°C, [r ] = 27.7 cm g" and P2 = 1.36 for aqueous solutions of this polymer. 

For 25 years, molecular dynamics simulations of proteins have provided detailed insights into the role of dynamics in biological activity and function [1-3]. The earliest simulations of proteins probed fast vibrational dynamics on a picosecond time scale. Fifteen years later, it proved possible to simulate protein dynamics on a nanosecond time scale. At present it is possible to simulate the dynamics of a solvated protein on the microsecond time scale [4]. These gains have been made through a combination of improved computer processing (Moore s law) and clever computational algorithms [5]. 

L Holm, C Sander. Evaluation of protein models by atomic solvation preference. J Mol Biol 225 93-105, 1992. 

RB Yelle, BW Beck, JB Koerner, CA Sacksteder, T Ichiye. Influence of the metal site on the structure and solvation of nibredoxm and its analogs A molecular dynamics study. Proteins accepted. 

The use of computer simulations to study internal motions and thermodynamic properties is receiving increased attention. One important use of the method is to provide a more fundamental understanding of the molecular information contained in various kinds of experiments on these complex systems. In the first part of this paper we review recent work in our laboratory concerned with the use of computer simulations for the interpretation of experimental probes of molecular structure and dynamics of proteins and nucleic acids. The interplay between computer simulations and three experimental techniques is emphasized (1) nuclear magnetic resonance relaxation spectroscopy, (2) refinement of macro-molecular x-ray structures, and (3) vibrational spectroscopy. The treatment of solvent effects in biopolymer simulations is a difficult problem. It is not possible to study systematically the effect of solvent conditions, e.g. added salt concentration, on biopolymer properties by means of simulations alone. In the last part of the paper we review a more analytical approach we have developed to study polyelectrolyte properties of solvated biopolymers. The results are compared with computer simulations. 

Proteins that are polyampholytes, upon addition of electrolyte, first undergo some salting in up to a certain ionic strength, since electrostatic interactions between ions are shielded by the additional simple ions of both sign. Adding more salt will then cause salting out as the added ions compete for water that would otherwise solvate the protein. 

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