A new force-field program for the calculation of glycopeptides and its application to a heptacosapeptide-decasaccharide of immunoglobulin G1.

Energetically favored conformations of glycopeptide I were calculated using the newly developed force-field program. GEGOP (geometry of glycopeptides). The three-dimensional structure of glycopeptide 1, which is part of the Fc fragment of IgG₁, has been calculated. I contains 27 amino acid residues from Pro291 to Lys317 and a biantennary decasaccharide N-linked to Ash297. The conformations of the peptide and the carbohydrate parts are shown to be mutually dependent. Single glycosyl residues of I exhibit interaction energies of up to -31.8 kJ/mol with the peptide portion. Generally, only a few of the glycosyl residues of the oligosaccharide moiety express significant interaction energies with the peptide parts. No easy prediction is possible of glycosyl residues which exhibit favorable interaction energies. However, in all of the calculated structures, the glycosyl residues of the 1 - 6-linked branches show strong attractive forces for the peptide part. 1 - 6-glycosidically linked branches can adopt a larger number of conformations than other linkages due to their high flexibility which allows more favorable interactions with proteins. We developed the GEGOP program in order to be able to study the preferred conformations of large glycopeptides. The program is based on the GSA (geometry of saccharides) program and utilizes the HSEA (hard sphere exo anomeric) force field for the carbohydrate cart and the ECEPP/2 (empirical conformation energy program for peptides} force field [Némethy. G., Pottle, M. S. & Scheraga, H. A. (1983) J. Phys. Chem. 87, 1883 1887] for the peptide part. The GEGOP program allows the simultaneous relaxation of all rotational degrees of freedom of these glycoconjugates during the energy optimization process. Thus. mutual interactions between glycosyl and amino acid residues can be studied in detail. [ABSTRACT FROM AUTHOR]