Electrostatic effects, proteins

The development of efficient algorithms and the sophisticated description of long-range electrostatic effects allow calculations on systems with 100 000 atoms and more, which address biochemical problems like membrane-bound protein complexes or the action of molecular machines . 

Electrostatic effects have long been recognized in commercial HPLC columns for SEC of proteins (15,21,22). The usual remedy is to add 100 mM salt to the mobile phase. This works here too the Lys and Asp peaks collapse into the Gly peak with 100 mM salt (Eig. 8.8). High concentrations of sodium sulfate were added to determine the role played in SEC by hydrophobic interactions (sodium sulfate, a structure-forming salt, strengthens such interactions). Sodium sulfate increased the retention only of the most hydrophobic amino acids to any extent, and then only when the concentration approached 1 M. Clearly, hydrophobic interaction cannot account for the elution order of amino acids on PolyHEA. 

FIGURE 6.10. Comparing the energetics of the EVB configurations in solution and in the active site of lysozyme. The calculations were done by using the PDLD and related models (Refs. 6 and 7) and they represent a study of a stepwise mechanism. The energetics of a more concerted pathway (e.g., that of Fig. 6.9) is almost identical to that of the stepwise mechanism and correlated in a similar way with the electrostatic effect of the protein. 

Figure 2-3. Protonated Schiff-base of retinal (PSBR) and computational models used in ONIOM QM QM calculations (left). Electrostatic effects of the surrounding protein on excitation energies in bacteriorhodopsin evaluated using TD-B3LYP Amber right). (Adapted from Vreven and Morokuma [37] (Copyright American Institute of Physics) and Vreven et al. [38], Reprinted with permission.)...

Since electrostatic effects dominate the thermodynamic cycle as shown in Figure 10-2, major development efforts have focused on the calculation of electrostatic energy for transferring the neutral and charged forms of the ionizable group from water with dielectric constant of about 80 to the protein with a low dielectric constant (see later discussions). This led to the development of continuum based models, where water and protein are described as uniform dielectric media, and enter into the linearized Poisson-Boltzmann (PB) electrostatic equation,... 

Lee K, Fitch CA, Lecomte JT, Garcfa-Moreno EB (2002) Electrostatic effects in highly charged proteins Salt sensitivity of pKa values of histidines in staphylococcal nuclease. Biochemistry 41 5656-5667. 

Mehler EL, Guarnieri F (1999) A self-consistent, microenvironment modulated screened coulomb potential approximation to calculate pH-dependent electrostatic effects in proteins. Biophys J 75 3-22. 

Warshel A, Sharmaa PK, Katoa M, Parson WW (2006) Modeling electrostatic effects in proteins. Biochim Biophys Acta 1764 1647—1676. 

X-ray crystallography, docking modes can be validated by various NMR techniques NOEs may be observed between the ligand and the receptor protein by heteronuclear-filtered NOE spectroscopy [51], chemical shift changes of protein resonances upon binding can be analyzed by simulation of shifts caused by ring currents and electrostatic effects [52], and saturation transfer difference measurements indicate which part of the ligand is in direct contact with the protein [52]. 

Retention of proteins in ion exchange chromatography is mainly caused by electrostatic effects. Because both the protein and the surface have an electrical double layer associated to it, there is an increase in entropy when the two surfaces approach each other. This is due to a release of counter ions from the two double layers when they overlap. The model that is discussed here is based on a solution of the linearized Poisson-Boltzmann for two oppositely charged planar surfaces. We also show the result from a model where the protein is considered as a sphere and the... 

The importance of electrostatic effects in protein structure and function has long been recognized (Tanford and Kirkwood, 1957 Peratz, 1978 Warshel and Russell, 1984 Rogers, 1989). It is generally believed that electrostatic field effects are among the first that come into play when two protein molecules approach each other. The reason for this is that electrostatic fields reach much further out than any other force fields that we associate with protein-protein interaction. It is reasonable to expect that motion in the combined electrostatic field of both molecules helps to orient the molecules for subsequent docking. 

Rnssell, A.J., Thomas, P.G. and Fersht, A.R. (1987) Electrostatic effects on modification of charged gronps in the active site cleft of snbtilisin by protein engineering. J. Mol Biol., 193, 803-813. 

Preference for the ds/irons-peptide bond in N-acylprolines, a condition for the stereochemistry of peptides and proteins, is governed mostly by steric factors due to substituents on C , by short-range electrostatic effects, and by intramolecular hydrogen bonding. 

Thus we note that cations (and anions) in proteins would have a very general effect on protein stability, either through cross-linking (similar to the effects of disulfide bridges) or through a general electrostatic effect... 

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