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

• Published in: Biophysical journal Vol. 72; no. 3; pp. 1109 - 1126
• Main Authors: Smart, O.S., Breed, J., Smith, G.R., Sansom, M.S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.1997
• Subjects: 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; Ion Channels - physiology; Models, Structural; Protein Conformation; Receptors, Nicotinic - chemistry; Reproducibility of Results; Software
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/S0006-3495(97)78760-5

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.