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PMID: 9138559 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A novel method for structure-based prediction of ion channel conductance properties.

Biophysical journal ·Vol. 72 ·No. 3 ·1997-03-00 ·Pages 1109-26

Smart OS, Breed J, Smith GR, Sansom MS

Abstract

A rapid and easy-to-use method of predicting the conductance of an ion channel from its three-dimensional structure is presented. The method combines the pore dimensions of the channel as measured in the HOLE program with an Ohmic model of conductance. An empirically based correction factor is then applied. The method yielded good results for six experimental channel structures (none of which were included in the training set) with predictions accurate to within an average factor of 1.62 to the true values. The predictive r2 was equal to 0.90, which is indicative of a good predictive ability. The procedure is used to validate model structures of alamethicin and phospholamban. Two genuine predictions for the conductance of channels with known structure but without reported conductances are given. A modification of the procedure that calculates the expected results for the effect of the addition of nonelectrolyte polymers on conductance is set out. Results for a cholera toxin B-subunit crystal structure agree well with the measured values. The difficulty in interpreting such studies is discussed, with the conclusion that measurements on channels of known structure are required.

MeSH Terms
Adenosine Triphosphatases/chemistry Alamethicin/chemistry Bacterial Outer Membrane Proteins/chemistry Calcium-Binding Proteins/chemistry Computer Simulation Electric Conductivity Escherichia coli Gramicidin/chemistry Ion Channels/chemistry,physiology Models, Structural Protein Conformation Receptors, Nicotinic/chemistry Reproducibility of Results Software
Chemicals
Bacterial Outer Membrane Proteins Calcium-Binding Proteins Ion Channels Receptors, Nicotinic phospholamban Gramicidin Alamethicin Adenosine Triphosphatases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Smart O S
Department of Crystallography, Birkbeck College, University of London, England. o.smart@mail.cryst.bbk.ac.uk; www: http://www.cryst.bbk.ac.uk/-ubcg8ab/smart.html
Breed J
Smith G R
Sansom M S
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1016/S0006-3495(97)78760-5
Email
o.smart@mail.cryst.bbk.ac.uk
Published
1997-03-00
Pages
1109-26
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1184496
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1016/S0006-3495(97)78760-5 PMC Full Text View journal details
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