PREDICTION OF CONFORMATION OF RAT GALANIN IN THE PRESENCE AND ABSENCEOF WATER WITH THE USE OF MONTE-CARLO METHODS AND THE ECEPP 3 FORCE-FIELD/

The conformation of the 29-residue rat galanin neuropeptide was studie d using the Monte Carlo with energy minimization (MCM) and electrostat ically driven Monte Carlo (EDMC) methods. According to a previously el aborated procedure, the polypeptide chain was first treated in a unite d-residue approximation, in order to enable extensive exploration of t he conformational space to be carried out (with the use of MCM). Then the low-energy united-residue conformations were converted to the all- atom representations, and EDMC simulations were carried out for the al l-atom polypeptide chains, using the ECEPP/3 force field with hydratio n included. In order to estimate the effect of environment on galanin conformation, the low-energy conformations obtained as a result of the se simulations were taken as starting structures for further EDMC runs that did not include hydration. The lowest-energy conformation obtain ed in aqueous solution calculations had a nonhelical N-terminal part p acked against the nonpolar face of a residual helix that extended from Pro(13) toward the C-terminus. One next lowest-energy structure was a nearly-all-helical conformation, but with a markedly higher energy. T n contrast, all of the low-energy conformations in the absence of wate r were all-helical differing only by the extent to which the helix was kinked around Pro(13). These results are in qualitative agreement wit h the available NMR and CD data of galanin in aqueous and nonaqueous s olvents.