Nature of Protein–CO₂ Interactions as Elucidated via Molecular Dynamics

Abstract

Rising global temperatures require innovative measures to reduce atmospheric concentrations of CO(2). The most successful carbon capture technology on Earth is the enzymatic capture of CO(2) and its sequestration in the form of glucose. Efforts to improve upon or mimic this naturally occurring process will require a rich understanding of protein-CO(2) interactions. Toward that end, extensive all-atom molecular dynamics (MD) simulations were performed on the CO(2)-utilizing enzyme phosphoenolpyruvate carboxykinase (PEPCK). Preliminary simulations were performed using implicit and explicit solvent models, which yielded similar results: arginine, lysine, tyrosine, and asparagine enhance the ability of a protein to bind carbon dioxide. Extensive explicit solvent simulations were performed for both wild-type PEPCK and five single-point PEPCK mutants, revealing three prevalent channels by which CO(2) enters (or exits) the active site cleft, as well as a fourth channel (observed only once), the existence of which can be rationalized in terms of the position of a key Arg residue. The strongest CO(2) binding sites in these simulations consist of appropriately positioned hydrogen bond donors and acceptors. Interactions between CO(2) and both Mn(2+) and Mg(2+) present in PEPCK are minimal due to the stable protein- and solvent-based coordination environments of these cations. His 232, suggested by X-ray crystallography as being a potential important CO(2) binding site, is indeed found to be particularly "CO(2)-philic" in these simulations. Finally, a recent mechanism, proposed on the basis of X-ray crystallography, for PEPCK active site lid closure is discussed in light of the MD trajectories. Overall, the results of this work will prove useful not only to scientists investigating PEPCK, but also to groups seeking to develop an environmentally benign, protein-based carbon capture, sequestration, and utilization system.

CO2Migration Pathways in Oxalate Decarboxylase and Clues about Its Active Site

“…On the basis of the nature of interactions of these (Arg, His, and Tyr) amino acids with CO 2 , these amino acids are called "CO 2 -philic" residues. 54 On the basis of mutation studies, Arg 92 was earlier proposed 19 to bind the substrate (oxalate); our results suggest that it can also bind the product CO 2 . The formate molecule was found to be bound to Arg 92 through strong hydrogen bonding interaction (see Figure S4 of the Supporting Information).…”

Estimating the binding ability of onium ions with CO2and π systems: a computational investigation

“…[23][24][25] For instance, Rosi and coworkers 26 have studied the CO 2 uptake capacity of MOFs through the cation exchange method, in the presence of methylated onium ions operating via various noncovalent interactions. Interestingly Cundari et al [27][28][29][30][31] concluded that acid-base interactions are the principal chemical force by which CO 2 binds to proteins.…”

Zeta-carbonic anhydrases show CS2 hydrolase activity: A new metabolic carbon acquisition pathway in diatoms?

“…Once identified the CO 2 binding site, the entry route for the substrate to the active site was also investigated by means of all-atom molecular dynamics (MD) simulations in explicit solvent. MD simulations have been widely used to investigate ligand migration paths inside proteins, also in the case of CO 2 ligand [39] , [40] , [41] but little is known on this topic for CAs, apart from few MD studies on hCA II isoform [42] , [43] , [44] . As first step, we employed CAVER program [33] to identify tunnels inside the protein, using the here reported X-ray structure of Zn-R3.…”