Atomistic molecular dynamics (MD) is frequently used to unravel the mechanisms of macroion release from electrosprayed droplets. However, atomistic MD is currently feasible for only the smallest window of droplet sizes appearing at the end steps of a droplet's lifetime. The relevance of the observations made to the actual droplet evolution, which is much longer that the simulated sizes, has not been addressed yet in the literature. Here, we perform a systematic study of desolvation mechanisms of poly(ethylene glycol) (PEG), protonated peptides of different compositions and proteins in order to (a) obtain insight into the charging mechanism of macromolecules in larger droplets than those that are currently amenable to atomistic MD, and (b) examine whether currently used atomistic modeling can establish the extrusion mechanism of proteins from droplets. To mimic larger droplets that are not amenable to MD modeling, we scale down the systems, by simulating a large droplet size relative to the macromolecule. MD of PEG charging reveals that above a critical droplet size, ions are available near the backbone of the macromolecule, but charging occurs only transiently by transfer of ions from the solvent to the macroion, while below the critical size, the capture of the ion from PEG has a lifetime sufficiently long for extrusion of a charged PEG from the aqueous droplet. This is the first report of the role of droplet curvature in the relation between macroion conformation and charging. Simulations of peptides with high degree of hydrophobicity show that partial extrusion of a peptide from the droplet surface is rare relative to desolvation by drying-out. Differently from what has been presented in the literature we argue that atomistic MD simulations have not sufficiently established extrusion mechanism of proteins from droplets and their charging mechanism. We also argue that release of highly charged proteins can occur at an earlier stage of a droplet's lifetime than predicted by atomistic MD. In this earlier stage, we emphasize the key role of jets emanating from a droplet at the point of charge-induced instability in the release of proteins.
Molecular dynamics using atomistic modeling is frequently used to extract the mechanisms of macroion release from electrosprayed droplets. However, atomistic modeling is currently feasible for only the smallest window of droplet sizes that omits the droplet history. The relevance of the observations made in this narrow window to the actual droplet evolution has not been addressed. Here, we perform a systematic study of desolvation mechanisms of poly(ethylene glycol) (PEG), protonated peptides of different compositions and protonated proteins in order to examine whether atomistic modeling can establish the extrusion mechanism of proteins from droplets. Atomistic modeling of PEG charging shows that above a critical droplet size charging occurs transiently by transfer of ions from the solvent to the macroion, while below the critical size, the capture of the ion from PEG has a lifetime sufficient for extrusion of the charged PEG from an aqueous droplet. This is the first report of the role of the droplet curvature in the charging of macroions. Modeling of the process in droplets of various sizes allow us to extrapolate the charging mechanisms in systems that cannot be modeled atomistically yet. Simulations even with highly hydrophobic peptides show that partial extrusion of a peptide from the droplet surface is rare relative to desolvation by drying-out of the protonated peptide. Differently from what has been presented in the literature we argue that atomistic simulations have not sufficiently established extrusion mechanism of proteins from droplets and their charging mechanism. Moreover, we argue that release of highly charged proteins can occur in earlier stage of a droplet's lifetime than that that is atomistically modeled. In this earlier stage, we emphasize the key role of jets emanating from a droplet at the point of charge-induced instability in the release of proteins.
Molecular dynamics using atomistic modeling is frequently used to extract the mechanisms of macroion release from electrosprayed droplets. However, atomistic modeling is currently feasible for only the smallest window of droplet sizes that omits the droplet history. The relevance of the observations made in this narrow window to the actual droplet evolution has not been addressed. Here, we perform a systematic study of desolvation mechanisms of poly(ethylene glycol) (PEG), protonated peptides of different compositions and protonated proteins in order to examine whether atomistic modeling can establish the extrusion mechanism of proteins from droplets. Atomistic modeling of PEG charging shows that above a critical droplet size charging occurs transiently by transfer of ions from the solvent to the macroion, while below the critical charge, the capture of the ion from PEG has a lifetime sufficient for extrusion of the charged PEG from an aqueous droplet. This is the first report of the role of the droplet curvature in the charging of macroions. Modeling of the process in droplets of various sizes allow us to extrapolate the charging mechanisms in systems that cannot be modeled atomistically yet. Simulations even with highly hydrophobic peptides show that partial extrusion of a peptide from the droplet surface is rare relative to desolvation by drying-out of the protonated peptide. Differently from what has been presented in the literature we argue that atomistic simulations have not sufficiently established extrusion mechanism of proteins from droplets and their charging mechanism. Moreover, we argue that release of highly charged proteins can occur in earlier stage of a droplet's lifetime than that that is atomistically modeled. In this earlier stage, we emphasize the key role of jets emanating from a droplet at the point of charge-induced instability in the release of proteins.
Atomistic molecular dynamics (MD) is frequently used to unravel the mechanisms of macroion release from electrosprayed droplets. However, atomistic MD is currently feasible for only the smallest window of droplet sizes appearing at the end steps of a droplet's lifetime. The relevance of the observations made to the actual droplet evolution, which is much longer than the simulated sizes, has not been addressed yet in the literature. Here, we perform a systematic study of the desolvation mechanisms of poly(ethylene glycol) (PEG), protonated peptides of different compositions, and proteins, to (a) obtain insight into the charging mechanism of macromolecules in larger droplets than those that are currently amenable to atomistic MD and (b) examine whether currently used atomistic MD modeling can establish the extrusion mechanism of proteins from droplets. To mimic larger droplets that are not amenable to MD modeling, we scale down the systems, by simulating a large droplet size relative to the macromolecule. MD of PEG charging reveals that, above a critical droplet size, ions are available near the backbone of the macromolecule, but charging occurs only transiently by transfer of ions from the solvent to the macroion, while below the critical size, the capture of the ion from PEG has a lifetime sufficiently long for the extrusion of a charged PEG from the aqueous droplet. This is the first report of the role of droplet curvature in the relation between macroion conformation and charging. Simulations of protonated peptides with a high degree of hydrophobicity show that partial extrusion of a peptide from the droplet surface is rare relative to desolvation by drying-out. Different from what has been presented in the literature, we argue that atomistic MD simulations have not sufficiently established the extrusion mechanism of proteins from droplets and their charging mechanism. We also argue that release of highly charged proteins can occur at an earlier stage of a droplet's lifetime than predicted by atomistic MD. In this earlier stage, we emphasize the key role of jets emanating from a droplet at the point of charge-induced instability in the release of proteins.
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