Flexible binding

One remarkable aspect of the EC structure is that, although both EpoA and PTX ligands occupy the same binding cavity, each one interacts with the amino acid side chains of the binding site in an unrelated and unique way. This fact rules out the hypothesis of a common pharmacophore for Epo and PTX. It may turn out to be a property of rather flexible binding pockets to accommodate different small molecules in detail differently. 

Dubey KD, Ojha RP (2012) Conformational flexibility, binding energy, role of salt bridge and alanine-mutagenesis for c-Abl kinase complex. J Mol Model 18(5)4679-1689... 

J. Apostolakis, A. Pluckthun, and A. Caflisch. Docking small ligands in flexible binding sites. Journal of Computational Chemistry, 19 21-37, 1998. 

The tertiary structure of a protein is the folding pattern of the secondary structural elements into a three-dimensional conformation, as shown for the LDH domain in Figure 7.8. As illustrated with examples below, this three-dimensional structure is designed to serve all aspects of the protein s function. It creates specific and flexible binding sites for ligands (the compound that binds), illustrated with actin and myoglobin. The tertiary structure also maintains residues on the surface appropriate for the protein s cellular location, polar residues for cytosolic proteins, and hydrophobic residues for transmembrane proteins (illustrated with the P2-adrenergic receptor). 

Recently, PI synthesis was accomplished by mutated PLD from Streptomyces anti-bioticus [32], Mutated PLD has a flexible binding substrate pocket that can recognize sterically hindered myo-inositol as a snbstrate. This successful result is supported by the evaluation of the catalytic molecular mechanism of PLD from Streptomyces sp. strain PMF [62], Application of mutagenesis to PLA2 holds considerable promise in the synthesis of novel types of PL containing various functional compounds. 

Prodock The program docks flexible hgands to a flexible binding site (representing the structure 16... 

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