Limits...
An entropic mechanism of generating selective ion binding in macromolecules.

Thomas M, Jayatilaka D, Corry B - PLoS Comput. Biol. (2013)

Bottom Line: Several mechanisms have been proposed to explain how ion channels and transporters distinguish between similar ions, a process crucial for maintaining proper cell function.Each operates in subtly different ways yet can produce markedly different influences on ion selectivity.Simple abstract-ligand models, as well as simple models based upon the ion binding sites in two amino acid transporters, show that limiting ligand fluctuations can create ion selectivity between Li(+), Na(+) and K(+) even when there is no strain associated with the molecular framework accommodating the different ions.

View Article: PubMed Central - PubMed

Affiliation: Research School of Biology, Australian National University, Canberra, Australia.

ABSTRACT
Several mechanisms have been proposed to explain how ion channels and transporters distinguish between similar ions, a process crucial for maintaining proper cell function. Of these, three can be broadly classed as mechanisms involving specific positional constraints on the ion coordinating ligands which arise through: a "rigid cavity", a 'strained cavity' and 'reduced ligand fluctuations'. Each operates in subtly different ways yet can produce markedly different influences on ion selectivity. Here we expand upon preliminary investigations into the reduced ligand fluctuation mechanism of ion selectivity by simulating how a series of model systems respond to a decrease in ligand thermal fluctuations while simultaneously maintaining optimal ion-ligand binding distances. Simple abstract-ligand models, as well as simple models based upon the ion binding sites in two amino acid transporters, show that limiting ligand fluctuations can create ion selectivity between Li(+), Na(+) and K(+) even when there is no strain associated with the molecular framework accommodating the different ions. Reducing the fluctuations in the position of the coordinating ligands contributes to selectivity toward the smaller of two ions as a consequence of entropic differences.

Show MeSH

Related in: MedlinePlus

A decomposition of(magenta), in the absence of cavity strain, into(black) and(brown) components of ion selectivity between Na+ and Li+ for (A) 4 fold, (B) 5 fold, (C) 6 fold and (D) 7 fold coordination states. The green region indicates a contribution toward Li+ selectivity, while the blue region indicates a contribution toward Na+ selectivity.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3585399&req=5

pcbi-1002914-g004: A decomposition of(magenta), in the absence of cavity strain, into(black) and(brown) components of ion selectivity between Na+ and Li+ for (A) 4 fold, (B) 5 fold, (C) 6 fold and (D) 7 fold coordination states. The green region indicates a contribution toward Li+ selectivity, while the blue region indicates a contribution toward Na+ selectivity.

Mentions: Having shown that restricting the fluctuations in the positions of the ligands creates selectivity for one ion over another even in the absence of strain, the question remains, how does this occur? If we decompose into the enthalpic, , and entropic, , components the driving force behind this change in selectivity becomes apparent. In the exchange between Na+ and K+ (Fig. 3) for and Na+ and Li+ (Fig. 4) for , the contribution follows very closely with indicating this selectivity is largely due to entropy differences. Intuitively one would expect the change in the available number of states (as you decrease the allowed fluctuations) to be largest for the larger ions for the following reasons. The number of possible configurations for coordination in the (only bound by a 3.5 Å constraining sphere) is greater for the larger ion than the smaller ion because of the greater volume available at the larger ion-ligand distance, as depicted in Fig. 5. As the positional restraint is increased (), the number of states become approximately equal for different ion types. Hence the change in entropy between a non-restrained and restrained system is largest for the larger ion. This can be shown to be the case by considering the difference in volume sampled by the coordinating oxygen atoms as their fluctuations becomes more and more constrained. For instance, this change in volume for the four fold coordination state is 3640 Å3 for Li+, 5050 Å3 for Na+ and 5820 Å3 for K+ when comparing and . Reducing the thermal fluctuations on the ligands causes a greater decrease in entropy when they coordinate a larger ion compared to a small one. As a consequence, this reduction of thermal fluctuations favours small ions binding in the site.


An entropic mechanism of generating selective ion binding in macromolecules.

Thomas M, Jayatilaka D, Corry B - PLoS Comput. Biol. (2013)

A decomposition of(magenta), in the absence of cavity strain, into(black) and(brown) components of ion selectivity between Na+ and Li+ for (A) 4 fold, (B) 5 fold, (C) 6 fold and (D) 7 fold coordination states. The green region indicates a contribution toward Li+ selectivity, while the blue region indicates a contribution toward Na+ selectivity.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585399&req=5

pcbi-1002914-g004: A decomposition of(magenta), in the absence of cavity strain, into(black) and(brown) components of ion selectivity between Na+ and Li+ for (A) 4 fold, (B) 5 fold, (C) 6 fold and (D) 7 fold coordination states. The green region indicates a contribution toward Li+ selectivity, while the blue region indicates a contribution toward Na+ selectivity.
Mentions: Having shown that restricting the fluctuations in the positions of the ligands creates selectivity for one ion over another even in the absence of strain, the question remains, how does this occur? If we decompose into the enthalpic, , and entropic, , components the driving force behind this change in selectivity becomes apparent. In the exchange between Na+ and K+ (Fig. 3) for and Na+ and Li+ (Fig. 4) for , the contribution follows very closely with indicating this selectivity is largely due to entropy differences. Intuitively one would expect the change in the available number of states (as you decrease the allowed fluctuations) to be largest for the larger ions for the following reasons. The number of possible configurations for coordination in the (only bound by a 3.5 Å constraining sphere) is greater for the larger ion than the smaller ion because of the greater volume available at the larger ion-ligand distance, as depicted in Fig. 5. As the positional restraint is increased (), the number of states become approximately equal for different ion types. Hence the change in entropy between a non-restrained and restrained system is largest for the larger ion. This can be shown to be the case by considering the difference in volume sampled by the coordinating oxygen atoms as their fluctuations becomes more and more constrained. For instance, this change in volume for the four fold coordination state is 3640 Å3 for Li+, 5050 Å3 for Na+ and 5820 Å3 for K+ when comparing and . Reducing the thermal fluctuations on the ligands causes a greater decrease in entropy when they coordinate a larger ion compared to a small one. As a consequence, this reduction of thermal fluctuations favours small ions binding in the site.

Bottom Line: Several mechanisms have been proposed to explain how ion channels and transporters distinguish between similar ions, a process crucial for maintaining proper cell function.Each operates in subtly different ways yet can produce markedly different influences on ion selectivity.Simple abstract-ligand models, as well as simple models based upon the ion binding sites in two amino acid transporters, show that limiting ligand fluctuations can create ion selectivity between Li(+), Na(+) and K(+) even when there is no strain associated with the molecular framework accommodating the different ions.

View Article: PubMed Central - PubMed

Affiliation: Research School of Biology, Australian National University, Canberra, Australia.

ABSTRACT
Several mechanisms have been proposed to explain how ion channels and transporters distinguish between similar ions, a process crucial for maintaining proper cell function. Of these, three can be broadly classed as mechanisms involving specific positional constraints on the ion coordinating ligands which arise through: a "rigid cavity", a 'strained cavity' and 'reduced ligand fluctuations'. Each operates in subtly different ways yet can produce markedly different influences on ion selectivity. Here we expand upon preliminary investigations into the reduced ligand fluctuation mechanism of ion selectivity by simulating how a series of model systems respond to a decrease in ligand thermal fluctuations while simultaneously maintaining optimal ion-ligand binding distances. Simple abstract-ligand models, as well as simple models based upon the ion binding sites in two amino acid transporters, show that limiting ligand fluctuations can create ion selectivity between Li(+), Na(+) and K(+) even when there is no strain associated with the molecular framework accommodating the different ions. Reducing the fluctuations in the position of the coordinating ligands contributes to selectivity toward the smaller of two ions as a consequence of entropic differences.

Show MeSH
Related in: MedlinePlus