Prediction of polyelectrolyte polypeptide structures using Monte Carlo conformational search methods with implicit solvation modeling

Many interesting proteins possess defined sequence stretches containing negatively charged amino acids. At present, experimental methods (X‐ray crystallography, NMR) have failed to provide structural data for many of these sequence domains. We have applied the dihedral probability grid‐Monte Carlo (DPG‐MC) conformational search algorithm to a series of N‐ and C‐capped polyelectrolyte peptides, (Glu)_(20), (Asp)_(20). (PSer)_(20), and (PSer‐Asp)_(10), that represent polyanionic regions in a number of important proteins, such as parathymosin, calsequestrin, the sodium channel protein, and the acidic biomineralization proteins. The atomic charges were estimated from charge equilibration and the valence and van der Waals parameters are from DREIDING. Solvation of the carboxylate and phosphate groups was treated using sodium counterions for each charged side chain (one Na^+ for COO^−; two Na for CO(PO_3)^(−2)) plus a distance‐dependent (shielded) dielectric constant, ϵ = ϵ_0R, to simulate solvent water. The structures of these polyelectrolyte polypeptides were obtained by the DPG‐MC conformational search with ϵ_0 = 10, followed by calculation of solvation energies for the lowest energy conformers using the protein dipole‐Langevin dipole method of Warshel