PROTEIN RECOGNITION OF ADENYLATE - AN EXAMPLE OF A FUZZY RECOGNITION TEMPLATE

The interaction between protein and adenylate in a non-homologous data set of 18 high-resolution protein/nucleotide crystal structures is ana lysed. We find that each constituent of adenylate, adenine, ribose and phosphate, is substantially buried. Adenine has a largely hydrophobic protein interface, while phosphate interacts primarily with hydrophil ic residues; ribose is intermediate. A detailed study of hydrogen bond ing in these complexes shows hydrogen bonds between protein and adenin e to be surprisingly scarce. There does not seem to be a conserved hyd rogen-bonding pattern for adenine recognition. The hydrogen bonds that are seen have geometries close to energy minima found in our Distribu ted Multipole Analysis based model calculations. The experimental hydr ogen-bonded geometries have a characteristic signature in our model en ergy calculations, with a dominant attractive electrostatic term. For stacked interactions, however, the dispersion energy dominates. Finall y, we present the concept of a fuzzy recognition template, as a useful means of describing the protein/adenylate interactions presented here , which will also be a valuable concept for characterising other prote in/ligand interactions. (C) 1996 Academic Press Limited