Protein-ligand interactions/complexes

Swegat, W. Schlitter, I. Kruger, R Wollmer, A., MD simulation of protein-ligand interaction formation and dissociation of an insulin-phenol complex, Biophys. J. 2003, 84, 1493-1506... 

Several kinetic parameters can be measured on different experimental systems to account for the interaction of a compound with CYPs. For example when studying the metabolic stability of a compound, it could be measured in a recombinant CYP system, in human liver microsomes, in hepatocytes and so on. Each system increases in biological complexity. Although in the recombinant CYP system only the cytochrome under consideration is studied, in the case of the human liver microsomes, there is a pool of enzyme present that includes several CYPs, and finally in the hepatocyte cell system, metabolizing enzymes play an important role in the metabolic compound stability. In addition, transport systems are also present that could involve recirculation or other transport phenomena. The more complex the experimental system, the more difficult it is to extract information on the protein/ligand interaction, albeit it is closer to the in vivo real situation and therefore to the mechanism that is actually working in the body. 

Protein-Ligand Interactions Exchange processes and determination of ligand conformation and protein-ligand contacts, 238, 657 nuclear magnetic studies of protein-peptide complexes,... 

A nerve impulse causes release of Ca2+ from the sarcoplasmic reticulum. The released Ca2+ binds to troponin (another protein-ligand interaction) and causes a conformational change in the tropomyosin-troponin complexes, exposing the myosin-binding sites on the thin filaments. Contraction follows. 

We have developed a profile-based approach termed p-SIFt [7] that enables us to describe the conservation of interactions between a set of protein-ligand receptor complexes. The use of profiles provides a sensitive means to compare and contrast multiple inhibitors binding to a drug target. A structural interaction fingerprint profile (p-SIFt) represents the degree to which interactions are conserved across a set of ligand-receptor complexes. The p-SIFt, P(r), is derived from an array, denoted below as b, of SIFt patterns and its derivation from a set of SIFts is shown in Fig. 10.2. 

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