Computational Analysis of Protein Tunnels and Channels
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Protein tunnels connecting the functional buried cavities with bulk solvent and protein channels, enabling the transport through biological membranes, represent the structural features that govern the exchange rates of ligands, ions, and water solvent. Tunnels and channels are present in a vast number of known proteins and provide control over their function. Modification of these structural features by protein engineering frequently provides proteins with improved properties. Here we present a detailed computational protocol employing the CAVER software that is applicable for: (1) the analysis of tunnels and channels in protein structures, and (2) the selection of hot-spot residues in tunnels or channels that can be mutagenized for improved activity, specificity, enantioselectivity, or stability.
Key wordsBinding Protein Tunnel Channel Gate Rational design Software CAVER Transport
The authors would like to express their thanks to Sergio Marques and David Bednar (Masaryk University, Brno) and to the editors Uwe Bornscheuer and Matthias Höhne (University Greifswald, Greifswald) for critical reading of the manuscript. MetaCentrum and CERIT-SC are acknowledged for providing access to supercomputing facilities (LM2015042 and LM2015085). The Czech Ministry of Education is acknowledged for funding (LQ1605, LO1214, LM2015051, LM2015047 and LM2015055). Funding has been also received from the European Union Horizon 2020 research and innovation program under the grant agreement No. 676559.
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