Protein binding, model for

Okonogi TM, Alley SC, Harwood EA, Hopkins PB, Robinson BH (2002) Phosphate backbone neutralization increases duplex DNA flexibility a model for protein binding. Proc Natl Acad Sci USA 99(7) 4156-4160... 

Williamson MP, Williams DH, Hammond SJ. Interactions of vancomycin and ristocetin with peptides as a model for protein binding. Tetrahedron 1984 40 569-573. 

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. 

The three-dimensional strucmres of Cro and of the lambda repressor protein have been determined by x-ray crystallography, and models for their binding and effecting the above-described molecular and genetic events have been proposed and tested. Both bind to DNA using hehx-turn-helix DNA binding domain motifs (see below). 

Fig. 4 HLM Clint, free vs clogD. HLM Clint, app corrected for microsomal protein binding using a computational model for microsomal binding. Open squares and filled triangles represent the same chemical series as in Fig. 3 (series A and B, respectively)...

Hoffman and collaborators (Doan et al. 1994) also performed ENDOR experiments on the oxidized [3Fe-4S] cluster in D. gigas hydrogenase. The authors detected resonances from strongly coupled protons which were assigned to the [3-CH2 of the cysteines and exchangeable protons that are probably involved in three different hydrogen bonds to the sulfurs of the cluster. Based on these data a model for the binding of the cluster to the protein was developed. 

Figure 10.3 The MWC model for the binding of ligands to a tetrameric protein. S = substrate T = tense conformation and R = relaxed conformation.

Figure 10.5 The KNF model for the binding of ligands to a tetrameric protein.

Extensive research on albumin has led to an increasingly clear picture of ligand binding. The dye phenol red has been widely used as a model for the binding of natural ligands to proteins. Experimental results have shown that each molecule of albumin binds at least six molecules of phenol red. The presence of fatty acids such as decanoate, palmitate, stearate, and oleate... 

Figure 2.149. (Liaison). Given a protein structure and series of ligands with known activities, Liaison uses the Linear Interaction (LIA) method to generate a model for predicting binding energies. In the example shown here, Liaison predicts the activities of 20 HIV-RT inhibitors with an accuracy of about 1 kcal/mol...

Zhang L, Gallicchio E, Levy RM (1999) Implicit Solvent Models for Protein-Ligand Binding, Insights Based on Explicit Solvent Simulations, (AIP Conference Proceedings, Simulation and Theory of Electrostatic Interactions in Solutions), 192 151 172... 

Jorgensen, W.L. (1991). Rusting of the lock and key model for protein-ligand binding. Science 254, 954 955. 

Figure 1 Model for collagen binding to platelets and the various binding proteins involved.

Schmidt am Busch M, Lopes A, Amara N, Bathelt C, Simonson T (2008) Testing the Coulomb/accessible surface area solvent model for protein stability, ligand binding, and protein design. BMC Bioinform 9 148-163... 

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