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On the zwitterionic nature of gas-phase peptides and protein ions.

Marchese R, Grandori R, Carloni P, Raugei S - PLoS Comput. Biol. (2010)

Bottom Line: Here we show that a novel computational protocol based on force field and massive density functional calculations is able to reproduce the experimental facets of well investigated systems, such as angiotensin II, bradykinin, and tryptophan-cage.The protocol takes into account all of the possible protomers compatible with a given charge state.Our calculations predict that the low charge states are zwitterions, because the stabilization due to intramolecular hydrogen bonding and salt-bridges can compensate for the thermodynamic penalty deriving from deprotonation of acid residues.

View Article: PubMed Central - PubMed

Affiliation: Statistical and Biological Physics Sector, International School for Advanced Studies (SISSA-ISAS) and DEMOCRITOS, Trieste, Italy.

ABSTRACT
Determining the total number of charged residues corresponding to a given value of net charge for peptides and proteins in gas phase is crucial for the interpretation of mass-spectrometry data, yet it is far from being understood. Here we show that a novel computational protocol based on force field and massive density functional calculations is able to reproduce the experimental facets of well investigated systems, such as angiotensin II, bradykinin, and tryptophan-cage. The protocol takes into account all of the possible protomers compatible with a given charge state. Our calculations predict that the low charge states are zwitterions, because the stabilization due to intramolecular hydrogen bonding and salt-bridges can compensate for the thermodynamic penalty deriving from deprotonation of acid residues. In contrast, high charge states may or may not be zwitterions because internal solvation might not compensate for the energy cost of charge separation.

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Related in: MedlinePlus

Energy/structure relationship for angiotensin II, bradykinin, and Trp-cage.The color scale refers to the average energy (kJ/mol) of polypeptides with the given pair of parameters.  stands for thermodynamic penalty to create a zwitterionic state expressed in terms of residues intrinsic gas-phase basicities (see text for the definition). In each panel, numbers indicate the location of lowest-energy protomers.
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pcbi-1000775-g002: Energy/structure relationship for angiotensin II, bradykinin, and Trp-cage.The color scale refers to the average energy (kJ/mol) of polypeptides with the given pair of parameters. stands for thermodynamic penalty to create a zwitterionic state expressed in terms of residues intrinsic gas-phase basicities (see text for the definition). In each panel, numbers indicate the location of lowest-energy protomers.

Mentions: Formation of charge separation between two residues is accompanied by a penalty. To a first approximation, this could be quantified in terms of the intrinsic GPB of the involved residues. The GPB of carboxylates is much higher than that of amino and guanidino groups (see Table 1 in Text S1). Therefore, charge separation between an acid, AH, and a base, B,is disfavored in the gas phase by a positive free-energy change (), where and stand for the intrinsic GPB of and B, respectively. The larger the , the larger the expected destabilization due to charge separation. In solution, solvation of the charged moieties may counterbalance this energetic penalty [36], [44]. The present results indicate that in the gas phase zwitterions can still be stabilized [3], [35], [38], [39], [51], [63], [111]. Indeed, the propensity of peptides to have a low energy correlates nicely with the number of ionized residues, as well as with (see Figure 2, first row, see also SI).For each charge state, values are relative to the protomer with the lowest charge separation for which has been set to zero. This is caused by the fact that intramolecular interactions can counterbalance this penalty [3], stabilizing the zwitterionic forms. In fact, such interactions, including (i) salt bridges and (ii) H-bonds, may reduce differences in the apparent GPB between basic residues and the conjugated base of acidic residues.


On the zwitterionic nature of gas-phase peptides and protein ions.

Marchese R, Grandori R, Carloni P, Raugei S - PLoS Comput. Biol. (2010)

Energy/structure relationship for angiotensin II, bradykinin, and Trp-cage.The color scale refers to the average energy (kJ/mol) of polypeptides with the given pair of parameters.  stands for thermodynamic penalty to create a zwitterionic state expressed in terms of residues intrinsic gas-phase basicities (see text for the definition). In each panel, numbers indicate the location of lowest-energy protomers.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2865515&req=5

pcbi-1000775-g002: Energy/structure relationship for angiotensin II, bradykinin, and Trp-cage.The color scale refers to the average energy (kJ/mol) of polypeptides with the given pair of parameters. stands for thermodynamic penalty to create a zwitterionic state expressed in terms of residues intrinsic gas-phase basicities (see text for the definition). In each panel, numbers indicate the location of lowest-energy protomers.
Mentions: Formation of charge separation between two residues is accompanied by a penalty. To a first approximation, this could be quantified in terms of the intrinsic GPB of the involved residues. The GPB of carboxylates is much higher than that of amino and guanidino groups (see Table 1 in Text S1). Therefore, charge separation between an acid, AH, and a base, B,is disfavored in the gas phase by a positive free-energy change (), where and stand for the intrinsic GPB of and B, respectively. The larger the , the larger the expected destabilization due to charge separation. In solution, solvation of the charged moieties may counterbalance this energetic penalty [36], [44]. The present results indicate that in the gas phase zwitterions can still be stabilized [3], [35], [38], [39], [51], [63], [111]. Indeed, the propensity of peptides to have a low energy correlates nicely with the number of ionized residues, as well as with (see Figure 2, first row, see also SI).For each charge state, values are relative to the protomer with the lowest charge separation for which has been set to zero. This is caused by the fact that intramolecular interactions can counterbalance this penalty [3], stabilizing the zwitterionic forms. In fact, such interactions, including (i) salt bridges and (ii) H-bonds, may reduce differences in the apparent GPB between basic residues and the conjugated base of acidic residues.

Bottom Line: Here we show that a novel computational protocol based on force field and massive density functional calculations is able to reproduce the experimental facets of well investigated systems, such as angiotensin II, bradykinin, and tryptophan-cage.The protocol takes into account all of the possible protomers compatible with a given charge state.Our calculations predict that the low charge states are zwitterions, because the stabilization due to intramolecular hydrogen bonding and salt-bridges can compensate for the thermodynamic penalty deriving from deprotonation of acid residues.

View Article: PubMed Central - PubMed

Affiliation: Statistical and Biological Physics Sector, International School for Advanced Studies (SISSA-ISAS) and DEMOCRITOS, Trieste, Italy.

ABSTRACT
Determining the total number of charged residues corresponding to a given value of net charge for peptides and proteins in gas phase is crucial for the interpretation of mass-spectrometry data, yet it is far from being understood. Here we show that a novel computational protocol based on force field and massive density functional calculations is able to reproduce the experimental facets of well investigated systems, such as angiotensin II, bradykinin, and tryptophan-cage. The protocol takes into account all of the possible protomers compatible with a given charge state. Our calculations predict that the low charge states are zwitterions, because the stabilization due to intramolecular hydrogen bonding and salt-bridges can compensate for the thermodynamic penalty deriving from deprotonation of acid residues. In contrast, high charge states may or may not be zwitterions because internal solvation might not compensate for the energy cost of charge separation.

Show MeSH
Related in: MedlinePlus