Protein electrostatics

PD Swartz, BW Beck, T Ichiye. Stiaictural origins of redox potential m iron-sulfur proteins Electrostatic potentials of crystal structures. Biophys 1 71 2958-2969, 1996. 

The charge of a number of proteins has been measured by titration. The early experimental work focused on the determination of charge as a function of pH later work focused on comparing the experimental and theoretical results the latter obtained from the extensions of the Tanford-Kirkwood models on the electrostatic behavior of proteins. Ed-sall and Wyman [104] discuss the early work on the electrostatics of polar molecules and ions in solution, considering fundamental coulombic interactions and accounting for the dielectric properties of the media. Tanford [383,384], and Tanford and Kirkwood [387] describe the development of the Tanford-Kirkwood theories of protein electrostatics. For more recent work on protein electrostatics see Lenhoff and coworkers [64,146,334]. 

Haggerty, L Lenhoff, AM, Relation of Protein Electrostatics Computations to Ion-Exchange and Electrophoretic Behavior, Journal of Physical Chemistry 95, 1472, 1991. 

Femtosecond spectroscopy has an ideal temporal resolution for the study of ultrafast water motions from femtosecond to picosecond time scales [33-36]. Femtosecond solvation dynamics is sensitive to both time and length scales and can be a good probe for protein hydration dynamics [16, 37-50]. Recent femtosecond studies by an extrinsic labeling of a protein with a dye molecule showed certain ultrafast water motions [37-42]. This kind of labeling usually relies on hydrophobic interactions, and the probe is typically located in the hydrophobic crevice. The resulting dynamics mostly reflects bound water behavior. The recent success of incorporating a synthetic fluorescent amino acid into the protein showed another way to probe protein electrostatic interactions [43, 48]. 

Figure 4-9. (a) HOMO and LUMO distributions of rhodopsin (Rh), (b) Protein-electrostatic potential at atoms in the retinal skeleton in atomic unit... 

Several computational models were employed in our study [35], Model I included a chromophore in gas-phase (Figure 4-10(a-d)). Model II additionally involved a point-charge model for protein electrostatic potential. In Model HI, the atoms in the active site (Figure 4-10(f)) were treated by quantum mechanics, and the rest of the protein effect was treated by the point-charge model. The structures used in Models... 

M. Neves-Petersen, S. Petersen, Protein electrostatics a review of the equations and methods used to model electrostatic equations in biomolecules - applications in biotechnology, Biotechnol. 

McLaughlin S, Murray D. Plasma membrane phosphoinositide organization by protein electrostatics. Nature 2005 438 605-611. 

A phosphoryl group adds two negative charges to a modified protein. Electrostatic interactions in the unmodified protein can be disrupted and new electrostatic interactions can be formed. Such structural changes can markedly alter substrate binding and catalytic activity. 

Electrostatics is one of the fundamental interactions that determine the structure, stability, binding affinity, chemical properties, and hence the biological reactivity, of proteins. Electrostatic interactions may contribute to the biological reactivity of proteins in a number of ways, which may be divided into the following general areas ... 

Combining Equations (1) and (5) for the protein electronic polarizability and the solvent polarizability, respectively, with Eqn. (10) for the field Warshel and co-workers (Lee et al. 1993 Warshel and Aqvist 1991 Warshel and Russell 1984) developed the Protein Dipole Langevin Dipole (PDLD) model which was the first consistent model for treating protein/solvent polarizabilities in protein electrostatic applications. The electrostatic field distribution in this model is given by... 

The Poisson-Boltzmann model is the. other major model for protein electrostatics, which has been widely used, especially because of its ability to treat salt effects. In applications, where the protein is not highly charged the Boltzmann term in Eqn. (15) can be linearized since e< >/kT < 1, giving... 

Holst, M., R. Kozack, F. Saied and S. Subramaniam. (1994a). Protein electrostatics-Rapid multigrid-based Newton algorithm for solution of the full nonlinear Poisson-Boltzmann equation. J. Biomol. Struct. Dynam. 11 1437-1445. 

The importance of protein electrostatics was pointed out and demonstrated by others quite early (e.g. Perutz, 1978 Hoi et al., 1978 Naray-Szaob, 1979) using more qualitative considerations, and it starts to be widely accepted (cf. e.g. Sharp and Honig, 1990). Here we will try to provide several examples for the importance of such effects in enzyme catalysis and in other aspects of protein action. We will try to distinguish between very qualitative treatments that do not consider the complete environment and quantitative ones treating it correctly. This is quite crucial, since the basic issue in enzyme catalysis is the actual magnitude of the given effect and not the assumption that it can be operative in some cases. 

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