Homology modeling and molecular dynamics study on N-acetylneuraminate lyase.

With homology modeling techniques, molecular mechanics and molecular dynamics methods, a 3D structure model of N-acetylneuraminate lyase from human (hNAL, EC 4.1.3.3) was created and refined. This model was further assessed by Profile-3D and PROCHECK, which confirms that the refined model is reliable. Furthermore, the docking results of the substrates (sialic acid and KDO) into the active site of hNAL indicate that hNAL can cleave the sialic acid and KDO. Thr51 and Tyr143 may be the key amino acids residues as they have strong hydrogen bonding interactions with the substrates, which is in good agreement with the experimental results by Izard et al. (Structure 2:361-369. doi:10.1016/S0969-2126(00)00038-1 (1994)). From the docking studies, we also suggest that Asp176 and Ser218 only form hydrogen bonds with sialic acid, therefore, they may help sialic acid interact with hNAL steadly.