CAVER 3.0: A tool for analysis of transport pathways in dynamic protein structures

E. Chovancová¹, A. Pavelka^1,2,3, P. Beneš², O. Strnad², J. Brezovský¹, B. Kozlíková², A. Gora¹, V. Šustr², M. Klvaňa¹, P. Medek², L. Biedermannová¹, J. Sochor², J. Damborský^1,3

¹Loschmidt Laboratories, Department of Experimental Biology and Centre for Toxic Compounds in the Environment, Faculty of Science, Masaryk University, Kamenice 5/A13, 625 00 Brno, Czech Republic

²Human Computer Interaction Laboratory, Faculty of Informatics, Masaryk University, Botanická 68a, 602 00 Brno, Czech Republic

³International Centre for Clinical Research, St. Anne's University Hospital Brno, Pekařská 53, 656 91 Brno, Czech Republic

akllupe@chemi.muni.cz

Tunnels and channels mediate the transport of ions and molecules in a large variety of proteins [1‑4]. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics, are essential for understanding of structure-function relationships of these proteins, and for the design of improved biocatalysts or new inhibitors [5]. Here, we present CAVER 3.0, a new tool for the geometry-based analysis of pathways in protein structures. CAVER 3.0 was designed to facilitate the analysis of static crystal structures as well as dynamical systems, and for this purpose it implements several new algorithms for calculation and clustering of pathways. In the input, users provide the protein structure or a set of aligned structures and specify calculation starting point. A number of additional settings are available, enabling users to adjust the calculation based on their needs. In the output, CAVER 3.0 provides all necessary data for the analysis of the time evolution of identified pathways, including the scripts for opening of the results in structure visualization software, information about pathway characteristics, amino acid composition and pathway profiles. Altogether, CAVER 3.0 enables an effective analysis of pathways in dynamic protein structures, which opens up new possibilities for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available as a multiplatform command-line application at http://www.caver.cz.

This work was financially supported by the European Regional Development Fund CZ.1.05/2.1.00/01.0001 and CZ.1.05/1.1.00/02.0123, and by the Czech Grant Agency P503/12/0572 and P202/10/1435.

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