Molecular dynamics simulation and quantum mechanical calculations on α-d-N-acetylneuraminic acid

N-Acetylneuraminic acid is a sugar molecule of biological significance due to its pivotal role in molecular recognition processes. The three dimensional structure and conformation of α-Neu5Ac in biological environments can be clearly observed by molecular dynamics (MD) simulation and quantum mechanical (QM) calculations. A 10 ns MD simulation on α-Neu5Ac yields two conformational models which are stabilized by water mediated hydrogen bond between O-8/O-9 hydroxyl oxygen and carbonyl of carboxylate group. The average life time of the conformers and the residual time of water which mediates the hydrogen bonding interactions are computed. Based on the amphiprotic nature of water, water mediation of each conformer is divided into two different modes, one donor–one acceptor mode and two donor modes. According to the analysis of simulation trajectories, the preferred mode of water mediation for conformers is the one donor–one acceptor mode. The energy and geometry of the MD derived conformational models of α-Neu5Ac are optimized using HF/6-31G∗ basis set of Gaussian03. QM calculations also resulted that α-Neu5Ac is preferentially stabilized by water mediated hydrogen bonding between O-8 hydroxyl and the carboxylate group where the mediation is one donor–one acceptor type. The optimized geometry of α-Neu5Ac which is in good agreement with the crystal structure of α-d-N-acetyl-1-O-methylneuraminic acid methyl ester is deposited in the public domain database 3DSDSCAR (http://3dsdscar.org). This optimized structure can be used by biotechnologists, biophysicists and glycobiologists for modelling the sialylglycans and also to design drugs using sialic acid analog inhibitors.

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► Conformational dynamics of α-Neu5Ac is crucial to molecular recognition processes.
► MD simulations yielded two conformational models stabilized by hydrogen bonding.
► Amphiprotic nature of water is considered in QM geometry optimization.
► Water donates one hydrogen to carboxylate and accepts one hydrogen from O-8 hydroxyl.
► Optimized structure is deposited at 3DSDSCAR database for public use.