On the Egress of Carbon Monoxide from Myoglobin

Abstract

The pathways of escape of carbon monoxide (CO) from sperm whale myoglobin were investigated by means of a biased form of all-atoms molecular dynamics (RAMD), whereby a weak, randomly oriented force is applied to the center of mass of CO. The force only persists if the direction taken by CO continues for a given period of time, otherwise a new direction is randomly chosen. A statistically significant number of RAMD runs gave distinct responses according to the level of approximations used for the model. Thus, with rigid bonds to all H-atoms, several portals for CO egress toward the solvent, besides the main H64 gate, were identified, like in recently published unbiased massive MD, six orders of magnitude acceleration of CO escape in RAMD notwithstanding. In contrast, by removing the approximation of rigid bonds in the model, only one of these extra portals was identified, besides the H64 portal. Sticking to this all-free-bonds model, Perutzs early suggestion that the H64 imidazole must rotate out toward the solvent in order that CO can cross the H64 gate was directly implemented. RAMD Simulations with this model led to CO egress from the H64 gate only, reconciling theory with experiments.

From Dioxygen Storing to Dioxygen Sensing with Neuroglobins: An Insight from Molecular Mechanics

“…The behavior described above for the mNgbÀCO system might recall the MgbÀCO system, which, with distal histidine in, toward iron, showed preference for NW egress [18]. However, with mNgÀCO, no tendency could be noticed for CO egress from the distal histidine gate, which, with Mgb, is about equally preferred to the NW gate, and becomes the sole gate when the distal histidine is turned out, toward the solvent [18].…”

“…Following the theoretical line to unravel CO and O 2 pathways inside the Ngbs, and compare them with both MgbÀCO [18] and CygbÀCO systems [17], recourse was made here to random-acceleration molecular dynamics (RAMD) [19], as conducted previously for the other two systems. Classical MD offers the most general approach to such problems, while RAMD alleviates the computational burden.…”

“…Classical MD offers the most general approach to such problems, while RAMD alleviates the computational burden. Studies with Mgb have also indicated that it is safe not to freeze any protein atom during the simulation [18]. With RAMD, a randomly-oriented small external force is applied to the center of mass of the ligand.…”

Gates and Binding Pockets for Nitric Oxide with Cytochrome c′, According to Molecular Dynamics

“…Present study of AXCPÀNO complexes has been carried out along RAMD simulations [13], as in previous examples of permeation of proteins by biologically relevant gases, concerning myoglobin [14], H-NOX [15], lipoxygenases [16], MauG [17], cytoglobin [18], heme oxygenase [19], and neuroglobins [20]. With RAMD simulations [13], a randomly oriented tiny force is applied to the center of mass of the ligand.…”

“…A large number of simulations should be carried out to attain statistical significance. In addition, according to our experience [14], no bond to any atom, except for the solvent medium, should be frozen during the simulation.…”