CAVER 3.0
| Authors | |
|---|---|
| Year of publication | 2011 |
| MU Faculty or unit | |
| Description | Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new inhibitors and construction of improved biocatalysts. CAVER is a software tool widely used for the identification and characterization of transport pathways in static macromolecular structures. Herein we present a new version of CAVER enabling automatic analysis of tunnels and channels in large ensembles of protein conformations from molecular dynamics simulations. CAVER 3.0 implements new algorithms for calculation and clustering of pathways. Trajectories from molecular dynamic simulations serve as the inputs, while detailed characteristics and summary statistics of the time evolution of individual pathways are provided in the outputs. To illustrate the capabilities of CAVER 3.0, the tool was applied to the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3 safely identified and reliably estimated the importance of all previously published DhaA pathways, including the pathways closed in DhaA crystal structures. Moreover, five examples of DhaA variants carrying substitutions in the bottleneck residues identified by CAVER 3.0 with substantially modified catalytic activity, binding affinity and kinetic stability are provided. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for estimation of pathway characteristics and elucidation of the structural basis of the tunnel gating. CAVER 3.0 paves the way for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available command-line application at http://www.caver.cz. |
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