CONFORMATION OF A CYCLIC HEPTAPEPTIDE IN SOLUTION - AN NMR CONSTRAINED DISTANCE GEOMETRY SEARCH PROCEDURE

A constrained distance geometry search procedure was used in conjunction with proton NMR data to determine the conformation of the cyclic heptapeptide evolidine, cyclo(Ser-Phe-Leu-Pro-Val-Asn-Leu), in dimethyl sulfoxide solution. Key features of the search procedure included more even sampling of dihedral angle space, generation of many conformations, exclusion of electrostatic interactions in energy minimization steps, and evaluation of possible conformations by their prediction of experimental data. With use of this procedure, two classes of closely related backbone conformations were identified for the cyclic heptapeptide. Both are similar to the recently determined crystal structure which can be described as containing a beta-bulge flanked by two beta-turns. Inclusion of electrostatic interactions in the energy minimization steps did not result in different backbone conformations provided that the NMR derived distance constraints were included. This latter result confirms that incorporation of NMR derived distance constraints can be an effective means of including solvent and electrostatic interactions in the conformational calculations for compounds in this size range.