Invitation: Seminar on Molecular Dynamics

You are cordially invited to a Seminar on:

Fatty Acids in Aqueous Solution: A Molecular Dynamics Study


Erwin P. Enriquez and Deniz P. Wong
Department of Chemistry
School of Science and Engineering,
Ateneo de Manila University
April 17, 2008, Thursday, 4:30-6:00 pm
Schmitt Hall C109


The aim of the study is to determine the unique feature of the C-12 fatty acid (lauric acid) in comparison with other fatty acids from C8 to C16 when dissolved inaqueous solution. This is motivated by the question: why the C-12 is the best length interms of the antimicrobial properties of the fatty acids, which in turn,might be linked to thegood medicinal properties of coconut oil (which is roughly 50% in C12).


ABSTRACT

A promising discovery about coconut oil is its anti-bacterial and anti-viral activity, which are believed to be due to its high (about 50 %) laurate (C-12) content.[1]-[2] There have been several hypotheses regarding this antimicrobial action—it is suggested that the fatty acid either destroys the lipid-coating that protects gram-positive bacteria or that it interferes with the signal transduction of viruses.[3] Further, it is still not clear why the C-12 among other fatty acids of other chain lengths has such an optimal antimicrobial property. One explanation is that the inhibitory fatty acid must be sufficiently water soluble to reach an effective concentration in the aqueous solution and yet hydrophobic enough to interact with the hydrophobic proteins or lipids on the microbial cell surface.[4]

Towards this inquiry, we embarked on a molecular dynamics (MD) investigation of a homologous series of fatty acids from C-8 to C-16 to observe any structural features that may be unique for C-12 when dissolved in aqueous solution. Molecular dynamics was done for a single fatty acid molecule (in carboxylate form) in a water box (using the TIP3P water model) with periodic boundary conditions. The MD software used was NAMD 2.6 which was run on a quad-core PC on a Windows XP platform. VegaZZ 2.1.0 was used to prepare the molecules prior to MD calculation, and analysis of the data was done using VMD 1.8.6.

The MD simulations reveal that all the fatty acid molecules were stable in a generally stretched conformation in aqueous solution during the 1 ns simulation runs. Qualitatively, one can argue that the conformational stability of the acid in water is due to three competing forces: (1) backbone strain, (2) hydration forces due to H-bonding or polar interactions, and (3) the hydrophobic effect. The hydrophobic effect is an entropic contribution to the stability of the system in order to minimize the ordering of water molecules surrounding a nonpolar region of a molecule.[5] The first effect is attributed to the conformational flexibility of the chain. On the other hand, the 2nd and 3rd effects should be evident in the structuring or ordering of water near the carboxylate end of the molecule (C1) and along the generally nonpolar alkyl backbone of the fatty acid (C2 to CN), respectively. The ordering of water in the hydration layers surrounding the fatty acid is evident in the so-called radial distribution functions g(r) of Cn-OH2O, which are calculated from the MD runs. The gives the average pair-wise separation of the Cn atom from the oxygen atoms of water (OH2O) in the simulation box. The stable folded length of the fatty acid due to these competing forces is also evident in the .
We hypothesize that the length of C-12 is indeed an optimal length that minimizes the effect of these three competing forces and that this may be demonstrated in the mapping of the g(r)’s along the backbone of the molecule. The results show high structuring of water at or near the polar carboxylate end group, as expected. There is also ordering of water near the methyl terminus and water “depletion” around the alkyl backbone, which are attributed to the hydrophobic effect.5

Selected References:

[1] Kabara, J., D. Swieczkowski, et al. Antimicrob. Agents Chemother., 1972, 2, 23-28.
[2] Bergsson, G., J. Arnfinnsson, et al. Antimicrob. Agents Chemother. 1998, 42, 2290-2294.
[3] Thormar, H., C. Issacs, et al. Antimicrob. Agents Chemother. 1987, 31, 27-31.
[4] Wang L. and E. Johnson Appl.and Environ. Microb. 1992, 58, 624-629
[5] Chandler, D. Nature 2005, 437, 640-647