Structure and function of channels and channelogs as studied by computational chemistry

Eisenman, George; Álvarez, Osvaldo

doi:10.1007/bf01871411

Cited by 34 publications

(24 citation statements)

References 90 publications

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“…Understanding the control of ion selectivity by ion channels is basically a problem in protein electrostatics (e.g., [172,173]) that turns out to be a truly challenging task. The primary problem is the evaluation of the free energy profile for transferring the given ion from water to the given position in the channel.…”

Section: Ion Channelsmentioning

confidence: 99%

Electrostatics of Proteins: Principles, Models and Applications

Braun‐Sand¹,

Warshel²

2005

Protein Folding Handbook

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Section: Ion Channelsmentioning

confidence: 99%

Electrostatics of Proteins: Principles, Models and Applications

Braun‐Sand¹,

Warshel²

2005

Protein Folding Handbook

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“…As discused by Furois-Corbin and Pullman (1989b) and by Eisenman and Alvarez (1991), with a channel formed by a bundle of parallel, or approximately parallel, helices, this energy profile is dominated by the effect of the aligned helix dipoles. The latter may be approximated by charges of + 1/2 at the N-termini and of -1/2 at the C-termini of the helices (Hol et al 1978).…”

Section: Ion Profiles and Helix Dipolesmentioning

confidence: 99%

“…As in an earlier paper (Sansom 1992) emphasis is placed upon obtaining a structural model of a given sequence motif, in this case the S/T-containing region of M2 helices. This investigation differs from attempts to model nAChR M2 helix bundles Pullman, 1989 a, b, 1991;Eisenman and Alvarez 1991;Stroud et al 1990) in that an isolated motif is investigated rather than complete M2 helices (plus adjacent residues). The modelling strategy employed is similar to that used in an earlier study of channel-forming peptides .…”

Section: Introductionmentioning

confidence: 99%

The roles of serine and threonine sidechains in ion channels: a modelling study

Sansom

1992

Eur Biophys J

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The ion channel of the nicotinic acetylcholine receptor (nAChR) is believed to be lined by transmembrane M2 helices. A "4-8-12" sequence motif, comprising serine (S) or threonine (T) residues at positions 4, 8 and 12 of M2, is conserved between different members, anion and cation selective, of the nAChR superfamily. Parallel bundles of 4-8-12 motif-containing helices are considered as simplified models of ion channels. The relationship between S and T sidechain conformations and channel-ion interactions is explored via evaluation of interaction energies of K+ and of Cl- ions with channel models. Energy calculations are used to determine optimal chi 2 (C alpha-C beta-O gamma-H gamma) values in the presence of K+ or Cl- ions. 4-8-12 motif-containing bundles may form favourable interactions with either cations or anions, dependent upon the chi 2 values adopted. Parallel-helix and tilted-helix bundles are considered, as are heteromeric models designed to mimic the Torpedo nAChR. The main conclusion of the study is that conformational flexibility at chi 2 enables both S and T residues to form favourable interactions with anions or cations. Consequently, there is apparently no difference between S and T residues in their interactions with permeant ions, which suggests that the presence of T vs. S residues within the 4-8-12 motif is not a major mechanism whereby anion/cation selectivity may be generated. The implications of these studies with respect to more elaborate models of nAChR and related receptors are considered.

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“…This requires explicit representation of the water molecules within the system, either using the Langevin dipole approximation (Warshel and Russell 1984), or via molecular dynamics simulations of the peptide plus water plus ion system (Mackay et al 1984; Aqvist and Warshel 1989; Roux and Karplus 1991). Eisenman and Alvarez (1991) have compared these two approaches in their studies of ion permeation through models of channel pores. Of course, to obtain a more complete representation of the system would require greater expenditure of computational time.…”

Section: K + Profile Evaluationmentioning

confidence: 99%

“…In particular, studies of channel-cation interactions are described. Related studies in this field have been carried out by Pullman (1989a, b, 1991), and by Eisenman and Alvarez (1991). Both of these groups have focused their attention on modelling the central pore region of the nicotinic acetylcholine receptor (nAChR).…”

Section: Introductionmentioning

confidence: 99%

Ion channels formed by amphipathic helical peptides

1991

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Channel forming peptides (CFPs) are amphipathic peptides, of length ca. 20 residues, which adopt an alpha-helical conformation in the presence of lipid bilayers and form ion channels with electrophysiological properties comparable to those of ion channel proteins. We have modelled CFP channels as bundles of parallel trans-bilayer helices surrounding a central ion-permeable pore. Ion-channel interactions have been explored via accessible surface area calculations, and via evaluation of changes in van der Waals and electrostatic energies as a K+ ion is translated along the length of the pore. Two CFPs have been modelled: (a) zervamicin-A1-16, a synthetic apolar peptaibol related to alamethicin, and (b) delta-toxin from Staphylococcus aureus. Both of these CFPs have previously been shown to form ion channels in planar lipid bilayers, and have been shown to have predominantly helical conformations. Zervamicin-A1-16 channels were modelled as bundles of 4 to 8 parallel helices. Two related helix bundle geometries were explored. K(+)-channel interactions have been shown to involve exposed backbone carbonyl oxygen atoms. delta-Toxin channels were modelled as bundles of 6 parallel helices. Residues Q3, D11 and D18 generate favourable K(+)-channel interactions. Rotation of W15 about its C beta-C gamma bond has been shown to be capable of occluding the central pore, and is discussed as a possible model for sidechain conformational changes in relation to ion channel gating.

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Structure and function of channels and channelogs as studied by computational chemistry

Cited by 34 publications

References 90 publications

Electrostatics of Proteins: Principles, Models and Applications

Electrostatics of Proteins: Principles, Models and Applications

The roles of serine and threonine sidechains in ion channels: a modelling study

Ion channels formed by amphipathic helical peptides

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