Protein ligand interactions

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

This experiment provides a nice example of the application of spectroscopy to biochemistry. After presenting the basic theory for the spectroscopic treatment of protein-ligand interactions, a procedure for characterizing the binding of methyl orange to bovine serum albumin is described. 

Van der Merwe A (2001) In Harding SE, Chowdhry BZ (eds) Protein-Ligand Interactions Hydrodynamics and Calorimetry. Oxford University Press, Oxford, UK, 137... 

As stated earlier, a commercially useful computational method must be fast, accurate, transferable, and interpretable. Logical steps one can take towards this goal are now presented. It is important to point out that under current resources, these four criteria cannot be simultaneously optimized. With current computational capabilities, the most complete theoretical description of protein-ligand interactions (which may involve many-body terms) cannot... 

Ferrara P, Gohlke H, Price DJ, Klebe G, Brooks CL. Assessing scoring functions for protein-ligand interactions. J Med Chem 2004 47 3032-47. 

As discussed in the introduction, scoring functions still pose problems (see also Chapter 14). Some of these problems arise from insufficient consideration of details of favorable and unfavorable protein-ligand interactions. 

Bohm HJ, Schneider G, editors. Protein-ligand interactions. From molecular recognition to drug design (Vol. 19 of Mannhold R, Kubinyi H, Foikers G, editors. Methods and Principles in Medicinal Chemistry). Weinheim Wiley-VCH, 2003. 

Muegge I, Martin YC. A general and fast scoring function for protein-ligand interactions a simplified potential approach. J Med Chem 1999 42 791-804. 

Gohlke H, Hendlich M, Klebe G. Knowledge-based scoring function to predict protein-ligand interactions. J Mol Biol 2000 295 337-56. 

Hendlich, M., Bergner, A., Gunther, Hebe, G. Design and development of a database for comprehensive analysis of protein-ligand interactions. /. Mol. Biol. 2003, 326, 607-620. 

Lee CK, Wang YM, Huang LS, Lin SM. 2007. Atomic force microscopy Determination of unbinding force, off rate and energy barrier for protein-ligand interaction. Micron 38 446-461. 

Methods that utilize structural data of the target, generally identified by protein crystallography, to look for molecules that complement the binding site through favorable protein-ligand interactions (protein structure-based VS or SBVS). 

Use of phage display to detect protein-ligand interactions... 

Figure 7.7. Protein microarray on polyvinylidene difluoride filters (PVDF). Proteins are gridded on filter and probed with an antibody to a gene of interest. Protein-ligand interactions could be detected using a labeled ligand as a probe.

Palzkill, T., Huang, W., and Weinstock, G. M. (1998). Mapping protein-ligand interactions using whole genome phage display libraries. Gene 221, 79-83. 

Wallace, A. C., R. A. Laskowski, and J. M. Thornton (1995). LIGPLOT A program to generate schematic diagrams of protein-ligand interactions. Protein Eng 8 127-134. 

This kind of shift mapping has been used extensively in NMR studies of protein-ligand interactions. Shuker et al.1/2 used this method to advantage in a lead generation approach that effectively covalently links two... 

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