Models ligand binding

LIGAND BINDING ANALYSIS Ligand binding model for positive coopera-tivity,... 

SCHEME 5.9 A residence time receptor-ligand binding model... 

T. G. Dewey, Biopolymers, 29, 1793 (1990). A Ligand Binding Model of Counterion Condensation to Finite Length Polyelectrolytes. 

Fig. 6 Structure of human galectin-3 CRD in complex with a lactose moiety bearing a lanthanide binding tag. Significant chemical shift perturbations (PCS) in the protein (residues represented as sticks) can be detected upon ligand binding (modelled from galectin structure PDB 2NN8).

We have previously calculated conformational free energy differences for a well-suited model system, the catalytic subunit of cAMP-dependent protein kinase (cAPK), which is the best characterized member of the protein kinase family. It has been crystallized in three different conformations and our main focus was on how ligand binding shifts the equilibrium among these ([Helms and McCammon 1997]). As an example using state-of-the-art computational techniques, we summarize the main conclusions of this study and discuss a variety of methods that may be used to extend this study into the dynamic regime of protein domain motion. 

Both the AFM rupture experiments as well as our simulation studies focussed on the streptavidin-biotin complex as a model system for specific ligand binding. Streptavidin is a particularly well-studied protein and binds its ligand biotin with high affinity and specificity [51]. Whereas previous experiments (see references in Ref. [49]) and simulation studies [52] referred only to bound/unbound states and the associated kinetics, the recent AFM... 

Fig. 13. Model for the ligand binding site of the receptor (87). The view of the receptor is from the extracellular face of the plasma...

The essential feature of the AAA is a comparison of active and inactive molecules. A commonly accepted hypothesis to explain the lack of activity of inactive molecules that possess the pharmacophoric conformation is that their molecular volume, when presenting the pharmacophore, exceeds the receptor excluded volume. This additional volume apparently is filled by the receptor and is unavailable for ligand binding this volume is termed the receptor essential volume [3]. Following this approach, the density maps for each of the inactive compounds (in their pharm conformations superimposed with that of active compounds) were constructed the difference between the combined inactive compound density maps and the receptor excluded volume represents the receptor essential volume. These receptor-mapping techniques supplied detailed topographical data that allowed a steric model of the D[ receptor site to be proposed. 

Analysis of Ligand Binding in the Intact Cell. A model of LR dynamics in the intact cell consistent with the results of these studies is presented in Figure 6, and a fit to the data of a polarization binding experiment is shown. The model has these characteristics ... 

Taylor NR, von Itzstein M (1994) Molecular modeling studies on ligand binding to sialidase from influenza virus and the mechanism of catalysis. J Med Chem 37 616-624... 

---