MD and DFT study of glycerol binding in B12-dependent diol dehydratase

During biodiesel production a large amount of glycerol is created as a byproduct [1, 2]. Dehydration of glycerol to a more valuable product could be obtained by eco-friendly methods utilizing B12-dependent dehydratases which turn glycerol into 3-hydroxypropanal [3-5]. However, the unusual property of glycerol is that it is both the supstrate and the irreversible inhibitor of B12-dependent dehydratases [6]. The proposed mechanism of inactivation is based on the crystal structure of B12-dependant diol dehydratase (DDH, PDB code: 3AUJ) [7]. This mechanism relies on the position of the hydroxyl group at C(3) atom of glycerol being oriented towards the serine residue (Ser301) in the active site. However, incompleteness of the enzyme in crystal structure (missing adenosyl group), poor resolution (2.1 Å) and small electron densityaroud C(3) call for further research. Herein we compare geometrical parameters of the active site of DDH obtained by molecular dynamic simulations (MD) and quantum chemical calculations (DFT) with the crystal structure, and investigate various patterns ofglycerol binding in the active site.