Proteins interaction

Evidence presented throughout the course of this review has emphasized the interaction of proteins and lipids in carrying out membrane-associated function. Thus, it is no longer admissible to conceive of lipids as acting merely as a matrix in which proteins exist rather, there is evidence that proteins can immobilize the lipids which bind them and that lipids can influence the temperature dependence of a number of membrane-protein functions. This mutual interaction of lipids and proteins is often viewed in the context of solvent effects. To a significant degree, this point of view derives from studies based on thermotropic phase transitions occurring in biomembranes. This subject has recently been discussed by Melchior and Steim (1976), Papa-hadjopoulos et al. (1975), and Lee (1977). They cite abundant evidence 

It is important to understand that the underlying biochemical cause for the discontinuities in the Arrhenius plots is not well understood. Moreover, the abrupt change seen in these plots should not be taken as an indication of a drastic change in behavior of a system as a consequence of addition of thermal energy. Rather, it is more likely that the discontinuity represents the initiation of a new phenomenon at that temperature. Hence, the actual physiologic effect at that temperature may be minimal. 

---

Figure Bl.20.10. Typical force curve for a streptavidin surface interacting with a biotin surface in an aqueous electrolyte of controlled pH. This result demonstrates the power of specific protein interactions. Reproduced with pennission from [81].

Leckband D ef a/1994 Direct force measurements of specific and nonspecific protein interactions S/oc/rem/sfry 33 4611-23... 

Direct ligand-protein interactions. Van der Waals and Coulomb energy of interaction of atoms of ligand with atoms on protein. 

Ligand-Protein Interactions The energy of formation of ligand-protein contacts can be computed as a sum of non-bonded (Lennard-Jones and electrostatic) terms similar to those used in a molecular dynamics simulation. 

The direct ligand-protein interactions and the net solvation-desolvation term together should give an energy contribution that strongly favors formation of the complex (large and negative), since the other two components favor its dissociation. 

Simulation Studies of Protein-Ligand Interactions 141 Table 2. Table Ligand-protein interaction energies and free energies (kcal/mol). 

Pearlman R S and K M Smith 1998. Novel Software Tools for Chemical Diversity. Perspectives in Dn Discovery and Design vols 9/10/ll(3D QSAR in Drug Design Ligand/Protein Interactions ar Molecular Similarity), pp. 339-353. 

In dye-binding tests, milk is mixed with excess acidic dye solution where the protein binds the dye in a constant ratio and forms a precipitate. After the dye—protein interaction takes place, the mixture is centrifuged and the optical density of the supernatant is determined. Utilization of the dye is thus measured and from it the protein content determined. Several methods for appHcation of dye-binding techniques to milk are given (24,25). 

Further investigations were carried out at lipid double layers and at phospholipids of membranes. Lipid-lipid and lipid-protein interactions were recognized by diazirine labeling (79PNA2595). 

To date, a number of simulation studies have been performed on nucleic acids and proteins using both AMBER and CHARMM. A direct comparison of crystal simulations of bovine pancreatic trypsin inliibitor show that the two force fields behave similarly, although differences in solvent-protein interactions are evident [24]. Side-by-side tests have also been performed on a DNA duplex, showing both force fields to be in reasonable agreement with experiment although significant, and different, problems were evident in both cases [25]. It should be noted that as of the writing of this chapter revised versions of both the AMBER and CHARMM nucleic acid force fields had become available. Several simulations of membranes have been performed with the CHARMM force field for both saturated [26] and unsaturated [27] lipids. The availability of both protein and nucleic acid parameters in AMBER and CHARMM allows for protein-nucleic acid complexes to be studied with both force fields (see Chapter 20), whereas protein-lipid (see Chapter 21) and DNA-lipid simulations can also be performed with CHARMM. 

Travers, A.A. DNA-Protein Interactions. London Chapman and Hall, 1990. 

These genetic experiments clearly demonstrated that the proposed structural model for the binding of these proteins to the phage operators was essentially correct. The second a helix in the helix-turn-helix motif is involved in recognizing operator sites as well as in the differential selection of operators by P22 Cro and repressor proteins. However, a note of caution is needed many other early models of DNA-protein interactions proved to be misleading, if not wrong. Modeling techniques are more sophisticated today but are still not infallible and are certainly not replacements for experimental determinations of structure. 

How is the binding specificity of the heterodimer achieved compared with the specificity of Mat a2 alone The crystal structure rules out the simple model that the contacts made between the Mat a2 homeodomain and DNA are altered as a result of heterodimerization. The contacts between the Mat o2 homeodomain and DNA in the heterodimer complex are virtually indistinguishable from those seen in the structure of the Mat o2 monomer bound to DNA. However, there are at least two significant factors that may account for the increased specificity of the heterodimer. First, the Mat al homeodomain makes significant contacts with the DNA, and the heterodimeric complex will therefore bind more tightly to sites that provide the contacts required by both partners. Second, site-directed mutagenesis experiments have shown that the protein-protein interactions involving the... 

No region of the cytochrome penetrates the membrane nevertheless, the cytochrome subunit is an integral part of this reaction center complex, held through protein-protein interactions similar to those in soluble globular multisubunit proteins. The protein-protein interactions that bind cytochrome in the reaction center of Rhodopseudomonas viridis are strong enough to survive the purification procedure. However, when the reaction center of Rhodohacter sphaeroides is isolated, the cytochrome is lost, even though the structures of the L, M, and H subunits are very similar in the two species. 

Michel. H., Epp, O., Deisenhofer, J. Pigment-protein interactions in the photosynthetic reaction center from Rhodopseudomonas viridis. EMBO f. 5 2445-2451, 1986. 

Yeates, T.O., et al. Structure of the reaction center from Rhodobacter sphaeroides R-26 membrane-protein interactions. Proc. Natl. Acad. Sci. USA 84 6438-6442, 1987. 

---