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Michelle Kuttel

Publications and source records attributed to Michelle Kuttel.

3 recordsLinked to original sources

Techniques for visualization of carbohydrate molecules.

Standard molecular visualizations, such as the classic ball-and-stick model, are not suitable for large, complex molecules because the overall molecular structure is obscured by the atomic detail. For proteins, the more abstract ribbon and cartoon representations are instead used to reveal large scale molecular conformation and connectivity. However, there is currently no accepted convention for simplifying oligo- and polysaccharide structures. We introduce two novel visualization algorithms for carbohydrates, incorporated into a visualization package, CarboHydra. Both algorithms highlight the sugar rings and backbone conformation of the carbohydrate chain, ignoring ring substituents. The first algorithm, termed PaperChain, emphasizes the type and conformation of the carbohydrate rings. The second, Twister, emphasizes the relative orientation of the rings. We further include two rendering enhancements to augment these visualizations: silhouettes edges and a translucent overlay of the ball-and-stick atomic representation. To demonstrate their utility, the algorithms and visualization enhancements are here applied to a variety of carbohydrate molecules. User evaluations indicate that they present a more useful view of carbohydrate structure than the standard ball-and-stick representation. The algorithms were found to be complementary, with PaperChain particularly effective for smaller carbohydrates and Twister useful at larger scales for highlighting the backbone twist of polysaccharides.

Algorithms↗

Glycosidic linkage rotations determine amylose stretching mechanism.

The primary mechanism for relieving tensile strain in alpha-linked polysaccharides (e.g., [alpha-d-Glc-(1-->4)alpha-d-Glc]n) is achieved by complex rotations of the glycosidic linkages. This is shown through computer simulations of atomic force microscopy stretching experiments in combination with free energy calculations of the unfolding pattern for amylose. The experimental force-extension curve is reproduced and analyzed to reveal that the chair-to-boat conversions play a smaller role than previously proposed.

Amylose↗

Carbohydrate solution simulations: producing a force field with experimentally consistent primary alcohol rotational frequencies and populations.

We present a CHARMM Carbohydrate Solution Force Field (CSFF) suitable for nanosecond molecular dynamics computer simulations. The force field was derived from a recently published sugar parameter set.1 Dihedral angle parameters for the primary alcohol as well as the secondary hydroxyl groups were adjusted. Free energy profiles of the hydroxymethyl group for two monosaccharides (beta-D-glucose and beta-D-galactose) were calculated using the new parameter set and compared with similar force fields. Equilibrium rotamer populations obtained from the CSFF are in excellent agreement with NMR data (glucose gg:gt:tg approximately 66:33:1 and galactose gg:gt:tg approximately 4:75:21). In addition, the primary alcohol rotational frequency is on the nanosecond time scale, which conforms to experimental observations. Equilibrium population distributions of the primary alcohol conformers for glucose and galactose are reached within 10 nanoseconds of molecular dynamics simulations. In addition, gas phase vibrational frequencies computed for beta-D-glucose using this force field compare well with experimental frequencies. Carbohydrate parameter sets that produce both conformational energies and rotational frequencies for the pyranose primary alcohol group that are consistent with experimental observations should allow for increased accuracy in modeling the flexibility of biologically important (1-6)-linked saccharides in solution.

Alcohols↗