CAVER 3.0: A Tool for the Analysis of Transport Pathways in Dynamic Protein Structures

By E. Chovancová, Antonín Pavelka, P. Benes, Ondřej Strnad, Jan Brezovsky, Barbora Kozliková, Artur Góra, Vilém Sustr, M. Klvaňa, Petr Medek and 3 more. PLoS Comput. Biol., 2012

1,284 citations recorded by the source corpus.

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. CAVER 3.0 implements new algorithms for the calculation and clustering of pathways. A trajectory from a molecular dynamics simulation serves as the typical input, 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 for the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3.0 safely identified and reliably estimated the importance of all previously published DhaA tunnels, including the tunnels closed in DhaA crystal structures. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for the 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 as a multiplatform command-line application at http://www.caver.cz.

Subfields: Materials Chemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ccda65d82cf4c4079947358837858b3e769b67ed

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Citations in the corpus

Using PyMOL as a platform for computational drug design (2017, background): “The characteristics of individual transport pathways, including their geometries and dynamic properties, can guide the design of novel drug candiates.(19) Additionally, the PyANM plugin allows its users to build and visualize anisotropic network models (ANM), a member of the elastic network models f”
Cryo-EM structures of human ZnT8 in both outward- and inward-facing conformations (2020, methodology): “The solvent accessible cavities were calculated with the program Caver (Chovancova et al., 2012).”
From primordial clocks to circadian oscillators (2023, methodology): “Tunnel detection and calculation were performed using CAVER 3.0.2 PyMOL plugin 61 , with the minimum probe radius varying between 0.9 and 1.1.”
Structure and dynamics of molecular networks: A novel paradigm of drug discovery: A comprehensive review (2012, background): “CAVER (http://caver.cz; Chovancova et al., 2012) uses molecular dynamics simulation to predict intra-protein transport pathways.”