TRANSBILAYER PORES FORMED BY BETA-BARRELS - MOLECULAR MODELING OF PORE STRUCTURES AND PROPERTIES

Transmembrane beta-barrels, first observed in bacterial porins, are possible models for a number of membrane channels. Restrained molecular dynamics simulations based on idealized C alpha beta templates have been used to generate models of such P-barrels. Model beta-barrels have been analyzed in terms of their conformational, energetic, and pore properties. Model beta-barrels formed by N = 4, 8, 12 and 16 anti-parallel Ala(10) strands have been developed. For each N, beta-barrels with shear numbers S = N to 2N have been modeled. In all beta-barrel models the constituent beta-strands adopt a pronounced right-handed twist. Interstrand interactions are of approximately equal stability for all models with N greater than or equal to 8, whereas such interactions are weaker for the N = 4 beta-barrels. In N = 4 beta-barrels the pore is too narrow (minimum radius similar to 0.6 Angstrom) to allow ion permeation. For N greater than or equal to 8, the pore radius depends on both N and S; for a given value of N an increase in S from N to 2N is predicted to result in an approximately threefold increase in pore conductance. Calculated maximal conductances for the beta-barrel models are compared with experimental values for porins and for K+ channels.