Molecular ligand-receptor complex

The interaction between ligands and their receptors is clearly a dynamic process. Once the static model of ligand-receptor interaction has been obtained, the stability of ligand-receptor complexes should be evaluated by means of molecular dynamics simulations [18]. 

Once the model of a ligand-receptor complex is built, its stability should be evaluated. Simple molecular mechanics optimization of the putative ligand-receptor complex leads only to the identification of the closest local minimum. However, molecular mechanics optimization of molecules lacks two crucial properties of real molecular systems temperature and, consequently, motion. Molecular dynamics studies the time-dependent evolution of coordinates of complex multimolecular systems as a function of inter- and intramolecular interactions (see Chapter 3). Because simulations are usually performed at nonnal temperature (—300 K), relatively low energy barriers, on the order of kT (0.6 kcal), can... 

Equation 6.19 predicts an increasing IC50 with either increases in L or 1. In systems with low-efficacy inverse agonists or in systems with low levels of constitutive activity, the observed location parameter is still a close estimate of the KB (equilibrium dissociation constant of the ligand-receptor complex, a molecular quantity that transcends test system type). In general, the observed potency of inverse agonists only defines the lower limit of affinity. 

So S-S. and M. Karplus (1999). A comparative study of ligand-receptor complex binding affinity prediction methods based on glycogen phosphorylase inhibitors. Journal of Computer Aided Molecular Design 13 243-258. 

Classen-Houben, D., Sippl, W., Holtje, H.-D. Molecular Modeling on Ligand-Receptor Complexes of Protein-Tyrosine-Phosphatase IB. In EuroQSAR 2002 Designing Drugs and Crop Protectants Processes, Problems and Solutions, Ford, M., Livingstone, D., Dearden, J., Van de Waterbeemd, H. (eds), Black-well, Bournemouth, 2002. 

Ligand-receptor interaction is an important initial step in protein function. The structure of ligand-receptor complex profoundly affects the specificity and efficiency of protein action. The molecular docking performs the computational prediction of... 

Figure 13.8. GPC followed by LC-MS-MS for screening mixtures of combinatorial libraries. After incubation of a receptor with a library of compounds, the ligand-receptor complexes (L-R) are separated from the low molecular weight unbound library compounds using GPC. Next, the L-R complexes are denatured during reversed phase HPLC to release the ligands for MS-MS identification.

Structure-activity relationships have been largely employed for molecular design these correlations depend on the molecular representation and the activity landscape. The molecular representation depends only on the small molecule, whereas the activity landscape provides information on the ligand-receptor complex, for example, how permissive the binding pocket is. To exemplify the molecular similarity approach, a set of odorants (compared to benzaldehyde) will be presented. 

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