Correlating Heme Potentials to the Physico-Chemical Properties of Their Binding Sites and Their Structural Distortion in Cytochromes by Clustering

Correlating Heme Potentials to the Physico-Chemical Properties of Their Binding Sites and Their Structural Distortion in Cytochromes by Clustering

In this paper, a clustering method was used to find out why the heme cofactor exhibits different potentials in cytochromes with a known 3-D structure. We have tried to find a relationship between heme potential in these proteins and the physico-chemical properties of amino acids in contact with their heme. We have also considered heme distortion which is a measure of out-of-plane distortion as another factor that can be induced by the protein structure. Heme proteins, particularly cytochrome b and cytochrome c, have been analyzed. Their ligand interaction sequences i.e. amino acids in contact with heme, were first determined by a protein software. We then defined the physico-chemical properties for the heme binding site by taking volume, hydrophilicity, area, polarity, hydrogen bonds, charge, shape, and buriability for each amino acid and summing them up. Heme distortion was also calculated by a computer program developed by John A. Shelnutt, which is available on-line. A literature survey was performed to find heme potentials. The cluster dendograms were created mathematically to identify the unique characteristics in each cytochrome from physico-chemical properties of their heme amino acid ligand sequences. Our findings will be applied to more complex proteins that have proven to be difficult to understand such as Cytochrome b6f. The idea is to understand how nature has utilized the same heme cofactor for various functions in cytochromes.