Conformational analysis of arachidonic and related fatty acids using molecular dynamics simulations.

Rich MR

Department of Biology, New York University, New York.

Biochim Biophys Acta 1178: 87-96 (1993)

Abstract
Arachidonic acid has recently gained attention as a result of current evidence indicating that it may play the role of a 'second messenger' in signal transduction processes. In order to gain insight into the mechanism behind its action, quenched molecular dynamics simulations were performed on arachidonic (20:4) and related fatty acids: linoleic (18:2), oleic (18:1), arachidic (20:0), and stearic (18:0). The angle-iron structure, representative of arachidonic acid in the crystal or very-low-temperature state, readily gave way at higher temperature to a dominant hairpin structure whereby the COOH end of arachidonic acid comes into close proximity with the C14-15 pi-bond resulting in a packed pi-bond-rich loop. The lowest energy conformer for arachidonic acid was found to be 10.65 kcal/mol below that of the energy-minimized crystal structure. In the case of saturated fatty acids, the crystal all-trans conformation remained the lowest energy form. Analysis of conformational energy contours for carbon-carbon torsion angles representative of fatty acids suggest that the flexibility of arachidonic acid is, in part, a result of the relative torsional freedom of C-C (single) bonds located between or adjacent to C = C (double) bonds. It is hypothesized that the ability of arachidonic acid to form packed structures with curved regions containing pi-bonds may allow for hydrophobic interactions with proteins, and/or hydrogen bonding between the pi-bonds of arachidonic acid and polar groups of the protein structures.

Mesh Headings

Arachidonic Acid*
Comparative Study
Computer Simulation
Linoleic Acids
Molecular Conformation
Oleic Acids
Signal Transduction
Stearic Acids
Thermodynamics

Unique Identifier: 93320126

Chemical Identifiers (Names)

(Linoleic Acids)
(Oleic Acids)
(Stearic Acids)
112-80-1 (oleic acid)
2197-37-7 (linoleic acid)
506-32-1 (Arachidonic Acid)
57-11-4 (stearic acid)