title: Fast assessment of structural models of ion channels based on their predicted current-voltage characteristics.
abstract: Computational prediction of protein structures is a difficult task, which involves fast and accurate evaluation of candidate model structures. We propose to enhance single-model quality assessment with a functionality evaluation phase for proteins whose quantitative functional characteristics are known. In particular, this idea can be applied to evaluation of structural models of ion channels, whose main function - conducting ions - can be quantitatively measured with the patch-clamp technique providing the current-voltage characteristics. The study was performed on a set of KcsA channel models obtained from complete and incomplete contact maps. A fast continuous electrodiffusion model was used for calculating the current-voltage characteristics of structural models. We found that the computed charge selectivity and total current were sensitive to structural and electrostatic quality of models. In practical terms, we show that evaluating predicted conductance values is an appropriate method to eliminate models with an occluded pore or with multiple erroneously created pores. Moreover, filtering models on the basis of their predicted charge selectivity results in a substantial enrichment of the candidate set in highly accurate models. Tests on three other ion channels indicate that, in addition to being a proof of the concept, our function-oriented single-model quality assessment method can be directly applied to evaluation of structural models of some classes of protein channels. Finally, our work raises an important question whether a computational validation of functionality should be included in the evaluation process of structural models, whenever possible.
authors.affiliation: Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, Wroclaw, 50-370, Poland.
authors.forename: Witold
authors.initials: W
authors.lastname: Dyrka
authors.affiliation: Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, Wroclaw, 50-370, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Kurczyńska
authors.affiliation: Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, Wroclaw, 50-370, Poland.
authors.forename: Bogumił M
authors.initials: BM
authors.lastname: Konopka
authors.affiliation: Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, Wroclaw, 50-370, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Kotulska
mesh_terms: D019295:Computational Biology; D007473:Ion Channels / Q000737:chemistry* / Q000502:physiology*; D008958:Models, Molecular; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D007473:Ion Channels
keywords: MQAP; Poisson-Nernst-Planck model; contact map; protein structure prediction; structure-function relationship