Protein structures contain highly complex systems of voids, making up specific features such as surface clefts or grooves, pockets, protrusions, cavities, pores or channels, and tunnels. Many of them are essential for the migration of solvents, ions and small molecules through proteins, and their binding to the functional sites. Analysis of these structural features is very important for understanding of structure-function relationships, for the design of potential inhibitors or proteins with improved functional properties. Here we critically review existing software tools specialized in rapid identification, visualization, analysis and design of protein tunnels and channels. The strengths and weaknesses of individual tools are reported together with examples of their applications for the analysis and engineering of various biological systems. This review can assist users with selecting a proper software tool for study of their biological problem as well as highlighting possible avenues for further development of existing tools. Development of novel descriptors representing not only geometry, but also electrostatics, hydrophobicity or dynamics, is needed for reliable identification of biologically relevant tunnels and channels.

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

References provided by Crossref.org

Caver Web 1.0: identification of tunnels and channels in proteins and analysis of ligand transport

HotSpot Wizard 2.0: automated design of site-specific mutations and smart libraries in protein engineering

MOLE 2.0: advanced approach for analysis of biomacromolecular channels

Gates of enzymes