Prediction of conformation of rat galanin in the presence and absence of water with the use of monte Carlo methods and the ECEPP/3 force field

The conformation of the 29-residue rat galanin neuropeptide was studied using the Monte Carlo with energy minimization (MCM) and electrostatically driven Monte Carlo (EDMC) methods. According to a previously elaborated procedure, the polypeptide chain was first treated in a united-residue approximation, in order to enable extensive exploration of the 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 all-atom polypeptide chains, using the ECEPP/3 force field with hydration included. In order to estimate the effect of environment on galanin conformation, the low-energy conformations obtained as a result of these simulations were taken as starting structures for further EDMC runs that did not include hydration. The lowest-energy conformation obtained in aqueous solution calculations had a nonhelical N-terminal part packed against the nonpolar face of a residual helix that extended from Pro¹³ toward the C-terminus. One next lowest-energy structure was a nearly-all-helical conformation, but with a markedly higher energy. In contrast, all of the low-energy conformations in the absence of water were all-helical differing only by the extent to which the helix was kinked around Pro¹³. These results are in qualitative agreement with the available NMR and CD data of galanin in aqueous and nonaqueous solvents.