ON THE COMPUTATION OF THE TERTIARY STRUCTURE OF GLOBULAR-PROTEINS .4. USE OF SECONDARY STRUCTURE INFORMATION

The distance geometry approach for computing the tertiary structure of globular proteins emphasized in this series of papers (Goel) is developed further. This development includes incorporation of some secondary structure information, the location of .alpha. helices in the primary sequence, in the algorithm to compute the tertiary structure of .alpha. helical globular proteins. An algorithm is developed which estimates the interresidue distances between chain-proximate helices. These distances, in conjuction with the global statistical average distances obtainable from a database of real proteins and determined by the primary sequence of the protein under study, are used to determine the tertiary structure. Five proteins, parvalbumin, hemerythrin, human Hb, lamprey Hb and sperm whale myoglobin, are investigated. The root mean square (RMS) errors between the calculated structures and those determined by X-ray diffraction range from 4.78-7.56 .ANG.. These RMSs are 0.21-2.76 .ANG. lower than those estimated without the secondary structure information. Contact maps and 3-dimensional backbone representations also show considerable improvements with introduction of secondary structure information.