Polypeptides molecules, as well as proteins, have a number of ionizable side-chain groups that can bind or release protons to become positively or negatively charged. The pKa of each ionizable group is, however, greatly influenced by the surrounded environment. Since charged groups may come spatially close to each other at intermediate conformations during folding, the equilibrium binding of protons depends on the polypeptide conformations and the environmental conditions. As consequence, calculations of the free energy of a polypeptide in solution should be based on the calculation of the solvation free energy and the free energy of equilibrium binding/releasing of protein. In order to consider explicitly the coupling of the ionization equilibrium, at a fixed pH, with the conformation during a molecular mechanic simulation we have use as model a 17-residue oligopeptide with sequence ETGTKAELLAKYEATHK with blocked ends. The Empirical Conformation Energy Program for Peptides (ECEPP/3) was used to generate the polypeptide chain and compute partially its energy (the one belong to form the molecule en vacuum). While the energy to transfer the molecule from vacuum to aqueous solution was computed using a new method to solve the Non Linear Poisson Boltzmann equation based upon the boundary element method (Vorobjev et.al., J.C.P., 1994, 98, 10940-10948). Considering that oligopeptides exist as an ensemble of low-energy conformations a large part of the work during this period was devoted to locate a set of low-energy structures in solution using EDMC method with different protocols. We will use this set to derive the relative conformational preference of the peptide at difference values of pH. The results will allow us to conclude about some aspects of the phenomena, such as the coupling between equilibrium ionization and helical conformational preference of oligopeptides. Computations were carried out using a parallel algorithm that runs on the IBM SP
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