Computational Studies on PA-IIL Lectin-Carbohydrate Interactions
N. K. Mishra,1 P. Kulhánek,1 Z. Kří,1 M. Wimmerová,1, 2 J. Koča1
1National Centre for Biomolecular Research and 2Department of Organic Chemistry, Faculty of Science, Masaryk University, Kotlářská 2, Brno 611 37.
Lectins are proteins of nonimmune origin that non-enzymatically selectively bind to mono or oligosaccharides. Multifarious activity of carbohydrates in biophysiological pathway, such as immune activity, tumor metastasis, cell-cell recognition, bacterial pathogenecity, open an avenue for the lectin-carbohydrate interaction research, which is also a big challenge for theoretical modeling due to the polar flexible saccharide moiety. One of the lectins, PA-IIL that produced by Pseudomonas aeruginosa, which play significant role in cystic fibrosis disease, motivated our study on PA-IIL-carbohydrate interactions.
The structure can provide a static view of the macromolecules, but for the full understanding of protein-ligand interactions it is necessary to know all the accessible spatial orientations of the ligand in the receptor binding pocket. It is often seen that the binding energy calculated over the sampled structure by molecular dynamics could give the insight of the interactions between protein and ligand.[1, 2] We used the MM/PBSA approach to calculate the binding free energy of the lectin-carbohydrate. The entropy contribution to the binding free energies was obtained by normal mode analysis. Unfortunately these conventional methods are not precise enough to accurately distinguish the binding order of saccharide series. Thus, to gain the insight of the spatial orientation of the monosaccharide and conversely the ligand induced fit in the receptor binding site, the binding energy and the pocket conform to the specific orientation of the saccharide was correlated. The spatial proximity of carbohydrate inside the binding domain is the key factor for the lectin-carbohydrate binding, which was identified by statistical clustering. One of the interesting finding was ions behavior, revealing their paramount significance for the binding.
1. Bonnet, P.; Bryce, R. A. Protein Sci. 2004, 13, 946-957.
2. P.J. Laitimen, T.; kankare, J. A.; Perakyla, M. Proteins: strucure, Function, and Bioinformatics 2004, 55, 34-43.