title: Refined models for the preferential interactions of tryptophan with phosphocholines.
abstract: A series of molecular models of the adducts formed between N-acetyl-l-tryptophan ethylamide and diacetyl-sn-glycero-3-phosphocholine have been generated. Using rOesy data that enabled us to place restrictions on the proximity of a number of key protons in the amino acid/phosphocholine pairs, a series of structures were generated following molecular dynamics and mechanics experiments using the CHARMM27 force field. These structures were then subjected to a series of clustering algorithms in order to classify the tight binding interactions between a single tryptophan and a phosphocholine. From these analyses, it is evident that: (i) binding is characterised by hydrogen bonding between the indole NH as donor and phosphate oxygen as acceptor, cation-carbonyl interactions between the choline ammonium and amide carbonyl groups and cation-pi interactions; (ii) cation-pi interactions are not always observed, particularly when their formation is at the expense of cation-carbonyl and hydrogen bonding interactions; (iii) on the basis of amino acid torsional parameters, it is possible to predict whether the phosphocholine headgroup will bind in a compact or elongated conformation. Extension of the procedures to characterise 2 : 1 Trp-PC binding revealed that the same intermolecular interactions are predominant; however, combinations of all three intermolecular interactions within the same adduct occur much more frequently due to the availability of donor/acceptor groups from both tryptophans in the 2 : 1 system.
authors.affiliation: Centre for Bioactive Chemistry, Department of Chemistry, University Science Laboratories, South Road, Durham, UK. j.m.sanderson@dur.ac.uk
authors.forename: John M
authors.initials: JM
authors.lastname: Sanderson
mesh_terms: D008055:Lipids / Q000737:chemistry; D008956:Models, Chemical; D008968:Molecular Conformation; D010767:Phosphorylcholine / Q000737:chemistry*; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D008055:Lipids; D010767:Phosphorylcholine; D014364:Tryptophan