Molecular dynamics study of the KcsA channel at 2.0-Å resolution: stability and concerted motions within the pore

Abstract

The stability of the KcsA channel accommodating more than one ion in the pore has been studied with molecular dynamics. We have used the very last X-ray structure of the KcsA channel at 2.0-A resolution determined by Zhou et al. [Nature 414 (2001) 43]. In this channel, six of the seven experimentally evidenced sites have been considered. We show that the protein remains very stable in the presence of four K+ ions (three in the selectivity filter and one in the cavity). The locations and the respective distances of the different K+ ions and water molecules (W), calculated within our KWKWKK sequence, also fits well with the experimental observations. The analysis of the K+ ions and water molecules displacements shows concerted file motions on the simulated time scale (approximately 1 ns), which could act as precursor to the diffusion of K+ ions inside the channel. A simple one-dimensional dynamical model is used to interpret the concerted motions of the ions and water molecules in the pore leading ultimately to ion transfer.

Differential Roles of Blocking Ions in KirBac1.1 Tetramer Stability

“…The crystal structures of KcsA, MthK, KvAP, and KirBac1.1 indicate that all these K ϩ channels share almost identical selectivity filter structures and very similar inner cavities lined by the M2 (S6) helices (7,8,33,34). It has long been recognized that complete removal of K ϩ will cause K ϩ channels to permanently lose their K ϩ selectivity or ion permeation capacity as a result of collapse or distortion of the selectivity filter (35)(36)(37), and molecular dynamics simulations suggest that the residence of K ϩ ions plays a critical role in stabilizing the structure of the selectivity filter of KcsA (9,12,21). Such a stabilizing effect conferred by the permeant ionoxygen ring coordination is likely a property of all K ϩ channels (11,21).…”

“…It has long been recognized that complete removal of K ϩ will cause K ϩ channels to permanently lose their K ϩ selectivity or ion permeation capacity as a result of collapse or distortion of the selectivity filter (35)(36)(37), and molecular dynamics simulations suggest that the residence of K ϩ ions plays a critical role in stabilizing the structure of the selectivity filter of KcsA (9,12,21). Such a stabilizing effect conferred by the permeant ionoxygen ring coordination is likely a property of all K ϩ channels (11,21). Krishnan et al (17) have shown that multiple permeant ions not only stabilize the selectivity filter but also stabilize the channel tetramer itself in KcsA.…”

“…In addition to protein-protein interaction between monomers, protein-lipid and protein-ion interactions play important roles in stabilizing the KcsA tetramer (17)(18)(19)(20). The selectivity filter of KcsA, coordinated with K ϩ ions, can serve as a bridge between the four monomers to maintain the structure of the selectivity filter and the tetrameric architecture of the channel as a whole (11,21). Blocking ions, such as Ba 2ϩ , also act as strong stabilizers (17).…”

Modeling the hERG potassium channel in a phospholipid bilayer: Molecular dynamics and drug docking studies

“…The correct positioning of the protein with respect to the bilayer is crucial for the success of the above-reported procedure, and this is usually achieved by maximizing the contacts between aromatic side chains and lipid headgroups. 63,64 However, the hERG primary sequence ranging from S5 to S6 did not allow this unbiased approach, therefore we preferred to first insert the well-studied KcsA template according to Carloni and coworkers, 64 and then to coherently superimpose the models (fitting against the SF Ca atoms: RMSD KcsA/hERG C 5 0.13 Å ; RMSD KcsA/hERG O 5 0.11 Å ).…”

Interaction and concerted diffusion of lithium in a (5,5) carbon nanotube

“…[68][69][70] This process often occurs when there is a mismatch between the equilibrium positions ͑minima͒ of the adsorbate-lattice interaction and the adsorbate-adsorbate interaction. 65,66 In situations where the adsorbate-adsorbate interaction is mainly repulsive, concerted diffusion can become viable if there are many metastable positions of the adsorbates with almost similar energies.…”