Exploring the ion selectivity properties of a large number of simplified binding site models.

Abstract:

:The ability to discriminate between different cations efficiently is essential for the proper physiological functioning of many membrane transport proteins. One obvious mechanism of ion selectivity is when a binding site is structurally constrained by the protein architecture and its geometry is precisely adapted to fit an ion of a given size. This mechanism is not effective in the case of flexible protein binding sites that are able to deform structurally or to adapt to a bound ion. In this study, the concept of nontrivial ion selectivity arising in a highly flexible protein binding site conceptually represented as a microdroplet of ligands confined to a small volume is explored. The environment imposed by the spatial confinement is a critical feature of the reduced models. A large number of reduced binding site models (1077) comprising typical ion-coordinating ligands (carbonyl, hydroxyl, carboxylate, water) are constructed and characterized for Na(+)/K(+) and Ca(2+)/Ba(2+) size selectivity using free energy perturbation molecular dynamics simulations. Free energies are highly correlated with the sum of ion-ligand and ligand-ligand mean interactions, but the relative balance of those two contributions is different for K(+)-selective and Na(+)-selective binding sites. The analysis indicates that both the number and the type of ligands are important factors in ion selectivity.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Roux B

doi

10.1016/j.bpj.2010.03.038

subject

Has Abstract

pub_date

2010-06-16 00:00:00

pages

2877-85

issue

12

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(10)00371-1

journal_volume

98

pub_type

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