CONFORMATIONAL-ANALYSIS OF THE 20-RESIDUE MEMBRANE-BOUND PORTION OF MELITTIN BY CONFORMATIONAL SPACE ANNEALING

The conformational space of the 20-residue membrane-bound portion of m elittin has been investigated extensively with the conformational spac e annealing (CSA) method and the ECEPP/3 (Empirical Conformational Ene rgy Program for Peptides) algorithm. Starting fi om random conformatio ns, the CSA method finds that there are at least five different classe s of conformations, within 4 kcal/mol, which have distinct backbone st ructures. We find that the lowest energy conformation of this peptide from previous investigations is not the global minimum-energy conforma tion (GMEC); but it belongs to the second lowest energy class of the f ive classes found here. In four independent runs one conformation is f ound repeatedly as the lowest energy conformation of the peptide (two of the four lowest energy conformations are identical; the other two h ave essentially identical backbone conformations brit slightly differe nt side-chain conformations). We propose this conformation, whose ener gy is lower than that found previously by 1.9 kcal/mol, as the GMEC of the ECEPP/3 force field. The structure of the proposed GMEC is less h elical and more compact than the previous one. It appears that the CSA method can find several classes of conformations of a 20-residue pept ide starting from random conformations utilizing only its amino acid s equence information. The proposed GMEC has also been found with a modi fied electrostatically driven Monte Carlo method [D. R. Ripoll, A. Liw o, and H. A. Scheraga (1998) ''New Developments of the Electrostatical ly Driven Monte Carlo Method: Test on the Membrane-Bound Portion of Me littin,'' Biopolymers, Vol. 46, pp. 117-126]. (C) 1998 John Wiley & So ns, Inc.