Refined models for the preferential interactions of tryptophan with phosphocholines

Sanderson, J.M.

Abstract

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– interactions; (ii) cation– 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.

Citation

Sanderson, J. (2007). Refined models for the preferential interactions of tryptophan with phosphocholines. Organic and Biomolecular Chemistry, 5(20), 3276- 3286. https://doi.org/10.1039/b707502b

• Journal Article Type: Article
• Publication Date: Jan 1, 2007
• Deposit Date: Jan 17, 2008
• Journal: Organic and Biomolecular Chemistry
• Print ISSN: 1477-0520
• Electronic ISSN: 1477-0539
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 5
• Issue: 20
• Pages: 3276- 3286
• DOI: https://doi.org/10.1039/b707502b
• Public URL: https://durham-repository.worktribe.com/output/1536098