title: Approach for the Simulation and Modeling of Flexible Rings: Application to the α-D-Arabinofuranoside Ring, a Key Constituent of Polysaccharides fromMycobacterium tuberculosis.
abstract: A number of lower organisms (bacteria, fungi, and parasites) produce glycoconjugates that contain furanose rings. Of particular interest to our group are cell wall polysaccharides from mycobacteria, including the human pathogen,Mycobacterium tuberculosis, which contain a large number of arabinofuranose resides. As part of a larger project on the conformational analysis of these molecules, we report here molecular dynamics simulations on methyl α-D-arabinofuranoside (1) using the AMBER force field and the GLYCAM carbohydrate parameter set. We initially studied the ability of this method to predict rotamer populations about the hydroxymethyl group (C4-C5) bond. Importantly, we show that simulation times of up to 200 ns 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 the furanoside ring by taking an average of the charges from a large number of conformers across the psuedorotational itinerary. The approach yields rotamer populations that are in good agreement with available NMR data and, in addition, provides insight into the nature of the puckering angle and amplitude in1.
authors.affiliation: Department of Chemistry and Alberta Ingenuity Centre for Carbohydrate Science, Gunning-Lemieux Chemistry Centre, University of Alberta, Edmonton AB T6G 2G2, Canada, and Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602.
authors.forename: Mikyung
authors.initials: M
authors.lastname: Seo
authors.affiliation: Department of Chemistry and Alberta Ingenuity Centre for Carbohydrate Science, Gunning-Lemieux Chemistry Centre, University of Alberta, Edmonton AB T6G 2G2, Canada, and Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602.
authors.forename: Norberto
authors.initials: N
authors.lastname: Castillo
authors.affiliation: Department of Chemistry and Alberta Ingenuity Centre for Carbohydrate Science, Gunning-Lemieux Chemistry Centre, University of Alberta, Edmonton AB T6G 2G2, Canada, and Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602.
authors.forename: Robert
authors.initials: R
authors.lastname: Ganzynkowicz
authors.affiliation: Department of Chemistry and Alberta Ingenuity Centre for Carbohydrate Science, Gunning-Lemieux Chemistry Centre, University of Alberta, Edmonton AB T6G 2G2, Canada, and Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602.
authors.forename: Charlisa R
authors.initials: CR
authors.lastname: Daniels
authors.affiliation: Department of Chemistry and Alberta Ingenuity Centre for Carbohydrate Science, Gunning-Lemieux Chemistry Centre, University of Alberta, Edmonton AB T6G 2G2, Canada, and Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Woods
authors.affiliation: Department of Chemistry and Alberta Ingenuity Centre for Carbohydrate Science, Gunning-Lemieux Chemistry Centre, University of Alberta, Edmonton AB T6G 2G2, Canada, and Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602.
authors.forename: Todd L
authors.initials: TL
authors.lastname: Lowary
authors.affiliation: Department of Chemistry and Alberta Ingenuity Centre for Carbohydrate Science, Gunning-Lemieux Chemistry Centre, University of Alberta, Edmonton AB T6G 2G2, Canada, and Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602.
authors.forename: Pierre-Nicholas
authors.initials: PN
authors.lastname: Roy