Conformational Analysis of Oligoarabinofuranosides: Overcoming Torsional Barriers with Umbrella Sampling

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• 作者：Shahidul M. Islam ; Michele R. Richards ; Hashem A. Taha ; Simon C. Byrns ; Todd L. Lowary ; Pierre-Nicholas Roy
• 刊名：Journal of Chemical Theory and Computation
• 出版年：2011
• 出版时间：September 13, 2011
• 年：2011
• 卷：7
• 期：9
• 页码：2989-3000
• 全文大小：1162K
• 年卷期：v.7,no.9(September 13, 2011)
• ISSN：1549-9626

文摘

In this report, the conformations of a series of mono- and oligoarabinofuranosides were probed through the use of umbrella sampling simulations with the AMBER force field and the GLYCAM carbohydrate parameter set. The rotamer population distribution about the exocyclic C4鈥揅5 bonds and the puckering distributions of the rings obtained from these umbrella sampling simulations were found to be in excellent agreement with those obtained from conventional long MD simulations for small monosaccharide fragments. For larger systems, the conventional MD approach becomes impractical, and we propose the use of umbrella sampling to circumvent poor sampling of certain conformations. The same umbrella sampling simulations were used to calculate the distributions about the vicinal protons and ensemble-averaged vicinal proton鈥損roton coupling constants (³J_H,H). The distributions about the vicinal protons of a monomer, methyl-伪-l-arabinofuranoside (1), were found to be very similar to those obtained from direct umbrella sampling simulations about the vicinal protons. We calculated ³J_H,H based on DFT-based Karplus-like relationships for l-arabinofuranosides. The ³J_H,H values were found to be very similar to those obtained with the conventional MD simulations. For 1, the ³J_H,H values obtained with the DFT-based Karplus equations agree very well with experimental results; the agreement is, however, not as good for the larger oligomers. An approach to determine the experimental rotamer populations from the simulations is also discussed.