Conformational statistics of the nitrogen linkage in glycopeptides using umbrella sampling

Abstract

The conformational statistics of the glycosylated dipeptide N - acetyl - δ - N - (2 - acetamido - β - D - glucopyranosyl) - L - asparaginyl - N' - methyl amide (glcNAc-Asn), a model of N-linked glycopeptides, was determined using umbrella sampling. The use of umbrella sampling allowed the importance sampling algorithm to accept new conformations with probabilities exceeding 40%. The satisfactory acceptance rate generated a chain of conformations and a set of properties suitable for comparison with available experimental results. Comparison of calculated structures for glcNAc-Asn with those determined experimentally by NMR, circular dichroism spectroscopy, and X-ray crystallography showed that the Momany-Scheraga conformation energy (ECEPP) over-emphasized non-bonded repulsions. Based on the experimentally determined structures, an effective two-fold potential barrier was imposed on the anomeric linkage. Predictions based on conformational statistics were sensitive to the choice of a three-fold or two-fold torsional barrier at the anomeric linkage.