Carbohydrate Force Fields: The Role of Small Partial Atomic Charges in Preventing Conformational Collapse.

Lazar, R. D. and Akher, F. B. and Ravenscroft, N. and Kuttel, M. M. (2022) Carbohydrate Force Fields: The Role of Small Partial Atomic Charges in Preventing Conformational Collapse., J. Chem. Theory Comput., 18, 1156-1172, American Chemical Society.

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Although the quality of current additive all-atom force fields for carbohydrates has been demonstrated in many applications, occasional significant differences reported for the hydrodynamic behavior of specific polysaccharides modeled with different force fields is a cause for concern. In particular, irreversible conformational collapse has been noted for some polysaccharide simulations with the GLYCAM06j force field. Here, we investigate the cause of this phenomenon through comparative simulations of a range of saccharides with both the GLYCAM06j and the CHARMM36 carbohydrate force fields. We find that conformational collapse in GLYCAM06j occurs for saccharide chains containing the deoxy sugar α-l-rhamnose after relatively long simulation intervals. Further, we explore the mechanism of conformational collapse and show that this phenomenon arises because of the anomalous low energy in GLYCAM06j (as compared to quantum mechanical calculations) of a specific orientation of α-l-Rha to α-l-Rha glycosidic linkages, which are subsequently sustained by intramolecular interactions in the saccharide chain. We identify the lack of partial charges on aliphatic hydrogens in GLYCAM as the source of this anomaly, demonstrating that addition of small partial atomic charges on the aliphatic protons in rhamnose removes the conformational collapse phenomenon. This work reveals the large cumulative impact that small partial charges may have on the dynamic behavior of polysaccharides and indicates that future reparameterization of the GLYCAM06j force field should investigate the addition of partial charges on all aliphatic hydrogens.

Item Type: Journal article (paginated)
Subjects: Computing methodologies > Modeling and simulation > Simulation types and techniques > Molecular simulation
Applied computing > Physical sciences and engineering > Chemistry
Date Deposited: 17 Sep 2022 08:51
Last Modified: 17 Sep 2022 08:51

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