QM Cluster or QM/MM in Computational Enzymology: The Test Case of LigW-Decarboxylase

Abstract

The catalytic mechanism of the decarboxylation of 5-carboxyvanillate by LigW producing vanillic acid has been studied by using QM cluster and hybrid QM/MM methodologies. In the QM cluster model, the environment of a small QM model is treated with a bulky potential while two QM/MM models studies include partial and full protein with and without explicitly treated water solvent. The studied reaction involves two sequential steps: the protonation of the carbon of the 5-carboxy-vanillate substrate and the decarboxylation of the intermediate from which results deprotonated vanillic acid as product. The structures and energetics obtained by using three structural models and two density functionals are quite consistent to each other. This indicates that the small QM cluster model of the presently considered enzymatic reaction is appropriate enough and the reaction is mainly influenced by the active site.

On the Catalytic Activity of the Engineered Coiled-Coil Heptamer Mimicking the Hydrolase Enzymes: Insights from a Computational Study

“…In order to investigate the catalytic mechanism, hybrid QM/MM procedure was applied as previously reported in similar systems [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. The QM region includes Cys18, His22 of the seven chains and Glu25 faced into the hydrophobic channel of the CC-Hept-Cys-His-Glu and three water molecules (w1, w2 and w3) engaged in a hydrogen bonds network (see Figure 4 ) both with each other and with the catalytic triad ( Figure S6 ).…”

“…The B3LYP/6-31+G(d,p) [ 46 , 47 ] and ff14SB [ 32 ] levels of theory were used for all geometry optimizations, for QM and MM regions respectively. Different previous works supported the use of B3LYP functional in enzymatic catalysis [ 10 , 11 , 12 , 13 , 48 , 49 ]. Full geometry optimizations and frequencies calculation for all the stationary points of the free energy surfaces were performed.…”

Mechanisms of metal-dependent non-redox decarboxylases from quantum chemical calculations

“… [43] This result lends further support to the mechanism proposed on the basis of the calculations. The mechanism shown in Scheme 2 a was subsequently corroborated by another computational study using a small active site model and two quantum mechanics/molecular mechanics (QM/MM) models [71] .…”

The Effects of the Metal Ion Substitution into the Active Site of Metalloenzymes: A Theoretical Insight on Some Selected Cases

“…Quantum mechanical electronic structure methods based on the density functional theory (DFT) were used to simulate the reactions catalyzed by metalloenzymes in the framework of quantum mechanics (QM) cluster approximation. This methodology was largely validated as a viable approach to explore enzymatic mechanisms and to give insights on the catalytic processes [28][29][30][31][32][33][34][35]. Moreover, the cluster modelling simulations represent a well-consolidated strategy to model transition states and to identify chemical mechanisms in calculations on small models of enzyme active sites as evidenced by the literature, [28,29,33,35] providing also detailed and fundamental chemical insights into metal-complex geometries and electronic structures [31][32][33][34][35][36][37].…”

“…This methodology was largely validated as a viable approach to explore enzymatic mechanisms and to give insights on the catalytic processes [28][29][30][31][32][33][34][35]. Moreover, the cluster modelling simulations represent a well-consolidated strategy to model transition states and to identify chemical mechanisms in calculations on small models of enzyme active sites as evidenced by the literature, [28,29,33,35] providing also detailed and fundamental chemical insights into metal-complex geometries and electronic structures [31][32][33][34][35][36][37]. Therefore, the choice to examine the three investigated enzymes by using the same cluster approach helps to emphasize the effects of the metal ion substitution in the active site.…”