Modeling the conformation of polyphenols and their complexation with polypeptides: self-association of catechin and its complexation with L-proline glycine oligomers.

Abstract

Over the past 10 years, several scientific thrusts have come together in the study of flavanoids that make it possible to move forward into the study of complexation between polyphenols and polypeptides. Enhanced understanding of the conformational properties of flavanoid monomers and polyflavanoids through molecular modeling, combined with the detailed NMR experimental data now in the literature, provide the foundation. Recent work using conformational searching techniques with the GMMX protocol has shown additional detail about the distribution of pseudo equatorial and pseudo low-energy axial conformers in the ensemble, as shown in figure 1. This leads to information about the relationship between the conformer ensemble and the Boltzmann averaged NMR proton coupling constants that one would expect to observe in a solution. Figure 1 also illustrates the pseudo equatorial to axial transformation that takes place in all catechin or (+)-catechin-(4 a ? 8)-(+)-catechin (B3) dimer complexes during the conformer searches and which would also be expected to occur in solution. Interest continues to further understand the details about this conformer distribution, as well as in the prediction of complexation of tannins with metal ions and proteins. Although the GMMX software has given many interesting results, it is limited in handling cases that require systematic conformational searching of molecules combined in a complex. In addition, there are no solvent model options.

Recent NMR studies on procyanidin dimers and NOE results of the complexation of L-proline-glycine compounds with (+)-catechin and polyflavanoid dimers have given data to help guide computational studies. Couple this with the improved molecular computational software available, and it becomes possible to explore complexation searching conformational space through Monte Carlo and molecular dynamics protocols using water as a solvent. The importance of this is highlighted by the renewed interest in its pharmacological characteristics such as the antiviral and antitumor behavior of tannins and other polyphenols, as well as reported interaction of polyphenols with proteins in aqueous solutions. In this chapter, the authors explore computational models for molecules such as L-proline-glycine and glycl-L-prolyl-glycl-glycine ion (GPGG ion) interacting with (+)-catechin and (+)-catechin-(4 a ? 8)-(+)-catechin (B3) to form complexes. These results are compared to the close-contact positions obtained from NOE NMR experiments in aqueous solution. The complex structures found using conformational search methods are discussed in terms of the specific hydrophobic and hydrophilic interactions observed.

Citation

Tobiason, Fred L.; Hemingway, Richard W.; Vergoten, Gerard. 1999. Modeling the conformation of polyphenols and their complexation with polypeptides: self-association of catechin and its complexation with L-proline glycine oligomers. In: Gross, Georg G.; Hemingway, Richard W.; Yoshida, Takashi, eds. Plant Polyphenols 2: Chemistry, Biology, Pharmacology, Ecology. New York: Kluwer Academic/Plenum Publishers: 527-544.