Ramachandran-type Plots for Glycosidic Linkages: Examples from Molecular Dynamics Simulations using the Glycam06 Force Field

The goals of this article are to (1) provide further validation of the Glycam06 force field, specifically for its use in implicit solvent molecular dynamic (MD) simulations, and (2) to present the extension of G.N. Ramachandran's idea of plotting amino acid phi and psi angles to the glycosidic phi, psi, and omega angles formed between carbohydrates. As in traditional Ramachandran plots, these carbohydrate Ramachandran-type (carb-Rama) plots reveal the coupling between the glycosidic angles by displaying the allowed and disallowed conformational space. Considering two-bond glycosidic linkages, there are 18 possible conformational regions that can be defined by (α, ϕ, ψ) and (β, ϕ, ψ), whereas for three-bond linkages, there are 54 possible regions that can be defined by (α, ϕ, ψ, ω) and (β, ϕ, ψ, ω). Illustrating these ideas are molecular dynamic simulations on an implicitly hydrated oligosaccharide (700 ns) and its eight constituent disaccharides (50 ns/disaccharide). For each linkage, we compare and contrast the oligosaccharide and respective disaccharide carb-Rama plots, validate the simulations and the Glycam06 force field through comparison to experimental data, and discuss the general trends observed in the plots.

Correlation of Pullout Force of Kirschner (K-) Wire to Other Factors Indicative of Bone Quality

More than 250,000 hip fractures occur annually in the United States and the most common fracture location is the femoral neck, the weakest region of the femur. Hip fixation surgery is conducted to repair hip fractures by using a Kirschner (K-) wire as a temporary guide for permanent bone screws. Variation has been observed in the force required to extract the K-wire from the femoral head during surgery. It is hypothesized that a relationship exists between the K-wire pullout force and the bone quality at the site of extraction. Currently, bone mineral density (BMD) is used as a predictor for bone quality and strength. However, BMD characterizes the entire skeletal system and does not account for localized bone quality and factors such as lifestyle, nutrition, and drug use. A patient’s BMD may not accurately describe the quality of bone at the site of fracture. This study aims to investigate a correlation between the force required to extract a K-wire from femoral head specimens and the quality of bone. A procedure to measure K-wire pullout force was developed and tested with pig femoral head specimens. The procedure was implemented on 8 human osteoarthritic femoral head specimens and the average pullout force for each ranged from 563.32 ± 240.38 N to 1041.01 ± 346.84 N. The data exhibited significant variation within and between each specimen and no statistically significant relationships were determined between pullout force and patient age, weight, height, BMI, inorganic to organic matter ratio, and BMD. A new testing fixture was designed and manufactured to merge the clinical and research environments by enabling the physician to extract the K-wire from each bone specimen himself. The new device allows the physician to gather tactile feedback on the relative ease of extraction while load history is recorded similar to the previous procedure for data acquisition. Future work will include testing human bones with the new device to further investigate correlations for predicting bone quality.