Development and validation of force-field parameters for molecular simulations of peptides and proteins containing open-shell residues

Parameters suitable for extending the AMBER force field for nucleic acids and proteins to open-shell derivatives of amino acid residues are proposed and tested. Two new atom types (radical carbon [CE] and hydrogen directly bonded to it [HE]) are introduced, whose parameters have been determined by a best fitting of quantum-mechanical computations of the simplest analogue of glycine radical (GlyR) in a peptide. The new force field is able to fit the reference results concerning both the structural parameters and the relative stabilities of the different conformers. It has been next applied to a conformational study of the distortions induced by extraction of the glycine Hα atom in an initially helical structure of a dodecamer of alanine including a central glycine residue. Our results show that the helical structure corresponds to a local energy minimum, but deeper minima are found which correspond to a fully planar GlyR residue included in a distorted helical sequence. © 1997 John Wiley & Sons, Inc. J Comput Chem18: 1720–1728, 1997