A study of procyanidin binding to Histatin 5 using Electrospray Ionization Tandem Mass Spectrometry (ESI-MS/MS) and molecular simulationsElectronic supplementary information (ESI) available. See DOI: 10.1039/c4cp05586a

• Main Authors: Shraberg, Joshua, Rick, Steven W, Rannulu, Nalaka, Cole, Richard B
• Format: Article
• Language: English
• ISSN: 1463-9076; 1463-9084
• DOI: 10.1039/c4cp05586a

Tannins act as antioxidants, anticarcinogens, cardio-protectants, anti-inflammatory and anti-microbial agents and bind to salivary peptides by hydrophilic and hydrophobic mechanisms. Electrospray Ionization Mass Spectrometry (ESI-MS) has been used to assess both hydrophilic and hydrophobic components of noncovalent binding in protein complexes. In the present study, direct infusion Electrospray-Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (ES-FTICR MS) is used to assess relative binding affinities of procyanidin tannin stereoisomers for salivary peptides arising from aqueous solutions. The condensed tannins procyanidin B1, B2, B3, and B4 demonstrate significantly different binding affinities for the salivary peptide Histatin 5. Rigid docking combined with molecular dynamics optimization is used to investigate procyanidin-Histatin 5 binding mechanisms and as a basis to rationalize trends found in the corresponding ES-FTICR MS experiments. The relative binding affinities of the four procyanidin rotamers are different in the gas and liquid phases. The simulation results indicate that many of the same contact points are made in both phases, but there is a increase in strong electrostatic interactions and an decrease in π-π contacts upon transfer from the liquid to the gas phase. The simulations reveal that the tannin interactions can make close contacts with a variety of amino acid residues on the peptide. First study correlating experimental mass spectrometry with computational simulations (gas and solution phases) that examines procyanidin binding to Histatin 5.