Modeling the Ion Selectivity of the Phosphate Specific Channel OprP

Abstract

Ion selectivity of transport systems is an essential property of membranes from living organisms. These entities are used to regulate multifarious biological processes by virtue of selective participation of specific ions in transport processes. To understand this process, we studied the phosphate selectivity of the OprP porin from Pseudomonas aeruginosa using all-atom free-energy molecular dynamics simulations. These calculations were performed to define the energetics of phosphate, sulfate, chloride, and potassium ion transport through OprP. Atomic-level analysis revealed that the overall electrostatic environment of the channel was responsible for the anion selectivity of the channel, whereas the particular balance of interactions between the permeating ions and water as well as channel residues drove the selectivity between different anions. The selectivity of OprP is discussed in light of well-studied ion channels that are highly selective for potassium or chloride.

Fosfomycin Permeation through the Outer Membrane Porin OmpF

“…The obtained results will be most interesting for studies of other porins with similar positively charged arginine ladders. Among these porins are the OmpF homologous or semihomologous OM Gram-negative bacterial proteins OmpC (68), PhoE (26), Omp32 (69), OmpK35/36 (70), OmpE35/ 36 (71), OprD (72), OprP (73), and OprO (74). Similar mechanisms as extracted here will likely apply, but especially for the narrower pores like OprD and OprP, the permeation rates will be much smaller than those for OmpF.…”

Structure, Dynamics, and Substrate Specificity of the OprO Porin from Pseudomonas aeruginosa

“…1). These arginine residues are believed to provide an electropositive sink to attract the phosphate ions from the dilute extracellular environment (13,18). Furthermore, on the periplasmic side of the channel, clusters of lysine residues (K30, K74, K15, 326, K109, and K126) are present as is also the case in OprP.…”

“…Either phosphate or diphosphate ions were subsequently placed at the mouth of the one of the monomers on the extracellular side for each porin. The monovalent form of the phosphate ion, H 2 PO 4 -, was investigated consistent with our previous studies (16)(17)(18), whereas the divalent form of the diphosphate ion, H 2 P 2 O 7 2was chosen as the most probable protonation state at pH 6. The systems were neutralized by addition of potassium ions and each system contained roughly 120,000 atoms.…”

“…Free-energy MD simulations were carried out to obtain the molecular details about the difference in the binding affinity of phosphate and diphosphate toward OprO and OprP. We already investigated the permeation of phosphate through OprP using free-energy MD simulations in a previous study (18).…”

“…Among these substrate-selective channels is OprP, a phosphate-selective porin that is induced under phosphate starvation conditions and facilitates the high-affinity acquisition of phosphate ions that are important for Pseudomonas growth and proliferation (7). A crystal structure of OprP is available (13) and detailed investigations have been carried out to understand the phosphate specificity of this interesting channel using bilayer electrophysiological measurements (6,14,15) and computational molecular dynamics (MD) simulations (16)(17)(18)(19).…”