Approach for the Simulation and Modeling of Flexible Rings: Application to the -D-Arabinofuranoside Ring, a K
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- 作者：Mikyung Seo ; Norberto Castillo ; Robert Ganzynkowicz ; Charlisa R. Daniels ; Robert J. Woods ; Todd L. Lowary ; Pierre-Nicholas Roy
- 刊名：Journal of Chemical Theory and Computation
- 出版年：2008
- 出版时间：January 2008
- 年：2008
- 卷：4
- 期：1
- 页码：184 - 191
- 全文大小：429K
- 年卷期：v.4,no.1(January 2008)
- ISSN：1549-9626
文摘
A number of lower organisms (bacteria, fungi, and parasites) produce glycoconjugatesthat contain furanose rings. Of particular interest to our group are cell wall polysaccharidesfrom mycobacteria, including the human pathogen, Mycobacterium tuberculosis, which containa large number of arabinofuranose resides. As part of a larger project on the conformationalanalysis of these molecules, we report here molecular dynamics simulations on methyl 
-D-arabinofuranoside (1) using the AMBER force field and the GLYCAM carbohydrate parameterset. We initially studied the ability of this method to predict rotamer populations about thehydroxymethyl group (C4-C5) bond. Importantly, we show that simulation times of up to 200ns are required in order to obtain convergence of the rotamer populations for this ring system.We also propose a new charge derivation approach that accounts for the flexibility of thefuranoside ring by taking an average of the charges from a large number of conformers acrossthe psuedorotational itinerary. The approach yields rotamer populations that are in goodagreement with available NMR data and, in addition, provides insight into the nature of thepuckering angle and amplitude in 1.
-D-arabinofuranoside (1) using the AMBER force field and the GLYCAM carbohydrate parameterset. We initially studied the ability of this method to predict rotamer populations about thehydroxymethyl group (C4-C5) bond. Importantly, we show that simulation times of up to 200ns are required in order to obtain convergence of the rotamer populations for this ring system.We also propose a new charge derivation approach that accounts for the flexibility of thefuranoside ring by taking an average of the charges from a large number of conformers acrossthe psuedorotational itinerary. The approach yields rotamer populations that are in goodagreement with available NMR data and, in addition, provides insight into the nature of thepuckering angle and amplitude in 1.