A program to construct chondroitin sulfate biopolymer models with biologically-relevant configurations

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Abstract Summary

Chondroitin sulfate (CS) is one of the most abundant proteoglycan carbohydrate biopolymers in the body and may contain hundreds of repeating disaccharide units. Atomic-resolution simulations of large systems are computationally taxing so we aimed to find a more efficient method of modeling biologically-relevant CS polymers. We developed a program that applies conformations from unbiased all-atom explicit-solvent molecular dynamics (MD) simulations of non-sulfated chondroitin 20-mers. Our program was used to construct non-sulfated chondroitin 20-mer models with conformations from MD-generated chondroitin 20-mers. We applied phi/psi dihedral angles of glycosidic linkages from MD-generated ensembles to our program and noticed a subtle difference in end-to-end distance distributions of constructed and MD-generated ensembles suggesting that there are other factors contributing to backbone flexibility. Next, we applied monosaccharide ring dihedrals from the MD-generated ensembles to our program and found that these contribute to end-to-end distance. Bond lengths and angles are also contributing factors and application of these data from MD-generated ensembles is necessary to produce biologically-relevant configurations. Each ring and linkage conformation was treated independently in construction so we checked for interactions between different linkages and rings by incorporating short simulations to minimize the energy of each configuration and examining resulting bond lengths. To validate application of 20-mer conformations to construct polymers of different lengths, we constructed chondroitin 10-mer ensembles and compared to 10-mer simulations. For each polymer length (20-mer and 10-mer), constructed and MD-generated ensembles had matching conformations and end-to-end distances indicating that our program can efficiently construct biologically-relevant CS polymer models of arbitrary length.

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Biomedical Sciences
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AM2 (11:00 - 12:00)