Abstract

Green tea is widely used in traditional oriental medicine for a variety of purposes and its active polyphenols, in particular (-)-Epigallocathechin 3-gallate (EGCg), have received recent experimental attention to ascertain whether the claimed health benefits, including to the heart, have scientific bases. We present a computational study of the structural and electronic properties of EGCg in vacuo, in aqueous solution and in interaction with the cardiac protein troponin C. Troponin is a complex of three proteins (I, C and T) playing an important role in the contractions of cardiac muscles. Muscle contractions and relaxations are controlled by variation in the levels of calcium, which binds to specific sites of troponin C. Hence, troponin C acts as a sort of contraction trigger for the cardiac muscle and is a potential target for drugs such as calcium (de)sensitizers for the treatment of heart diseases. The interaction of EGCg with troponin C has been recently studied by NMR spectroscopy to elucidate its potential as a modulator of heart contractions. We have used a range of simulation techniques including ligand-protein docking, molecular dynamics and metadynamics to reveal the microscopic details of such interaction and of potential mechanisms of action.