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. 2024 Jan 5;52(D1):D413-D418.
doi: 10.1093/nar/gkad1012.

ChannelsDB 2.0: a comprehensive database of protein tunnels and pores in AlphaFold era

Anna Špačková  1 , Ondřej Vávra  2   3 , Tomáš Raček  4   5 , Václav Bazgier  1 , David Sehnal  4   5 , Jiří Damborský  2   3 , Radka Svobodová  4   5 , David Bednář  2   3 , Karel Berka  1
Affiliations

ChannelsDB 2.0: a comprehensive database of protein tunnels and pores in AlphaFold era

Anna Špačková et al. Nucleic Acids Res. .

Abstract

ChannelsDB 2.0 is an updated database providing structural information about the position, geometry and physicochemical properties of protein channels-tunnels and pores-within deposited biomacromolecular structures from PDB and AlphaFoldDB databases. The newly deposited information originated from several sources. Firstly, we included data calculated using a popular CAVER tool to complement the data obtained using original MOLE tool for detection and analysis of protein tunnels and pores. Secondly, we added tunnels starting from cofactors within the AlphaFill database to enlarge the scope of the database to protein models based on Uniprot. This has enlarged available channel annotations ∼4.6 times as of 1 September 2023. The database stores information about geometrical features, e.g. length and radius, and physico-chemical properties based on channel-lining amino acids. The stored data are interlinked with the available UniProt mutation annotation data. ChannelsDB 2.0 provides an excellent resource for deep analysis of the role of biomacromolecular tunnels and pores. The database is available free of charge: https://channelsdb2.biodata.ceitec.cz.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
The growth of the content of ChannelsDB from the original version released in 2018 (9) to the current day (this study). The colour coding indicates different data categories - light coloured are MOLE calculated entries, and CAVER is a darker colour. The updated database ChannelDB 2.0 contains three times more data than the original release from 2018. The database has grown approximately ∼4.6 times in size of channel annotations. Calculation and visualisation of tunnels and channels using MOLE 2.0 is newly complemented by analysis using CAVER 3.02, thus allowing utilisation of consensus tunnel annotation.
Figure 2.
Figure 2.
Comparison of named reviewed cytochrome P450 2D6 tunnels from X-ray structure (left, PDB ID 3TBG) from Wang et al. (20) with automatically calculated tunnels from AlphaFill model (right, UniProt ID P10635). The structure is oriented from the membrane perspective (see the position of the transmembrane anchor in the AlphaFill model pointing towards the viewer), and thus, the major substrate entry tunnels (2b, 2e and 2f) are the most visible and retained in the AlphaFill model. Also, major product release tunnels (2c and S) pointing above the membrane (and sidewise for the viewer) are retained. A narrower rare egress tunnel 3 and water channel (W) leading to the proximal side toward the cytosol are missing. As seen from the tunnel 2b profile at the bottom of the figure, the profiles and their properties are almost identical, including channel-lining residues (bottom right) and their UniProt annotation (e.g. Phe 120 in chain A). All ligands in both structures were hidden for clarity.
Figure 3.
Figure 3.
Visualisation of tunnels identified in the structure of haloalkane dehalogenase LinB (PDB ID: 2BFN). (A) Reviewed tunnels extracted from the publication by Brezovsky et al. (26), tunnels calculated based on starting points defined by an automatic pipeline using the information about bound and cognate ligands with (B) MOLE 2.0 and (C) CAVER 3.02. Even with the automatically generated starting points and default settings, both tools correctly identified the main tunnel p1 and the slot tunnel p2.
See this image and copyright information in PMC

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