LifeSoaks: a tool for analyzing solvent channels in protein crystals and obstacles for soaking experiments.

Autor: Pletzer-Zelgert J; Center for Bioinformatics, Universität Hamburg, Bundesstrasse 43, 20146 Hamburg, Germany., Ehrt C; Center for Bioinformatics, Universität Hamburg, Bundesstrasse 43, 20146 Hamburg, Germany., Fender I; Center for Bioinformatics, Universität Hamburg, Bundesstrasse 43, 20146 Hamburg, Germany., Griewel A; Center for Bioinformatics, Universität Hamburg, Bundesstrasse 43, 20146 Hamburg, Germany., Flachsenberg F; Center for Bioinformatics, Universität Hamburg, Bundesstrasse 43, 20146 Hamburg, Germany., Klebe G; Institut für Pharmazeutische Chemie, Universität Marburg, Marbacher Weg 6-10, 35032 Marburg, Germany., Rarey M; Center for Bioinformatics, Universität Hamburg, Bundesstrasse 43, 20146 Hamburg, Germany.
Jazyk: angličtina
Zdroj: Acta crystallographica. Section D, Structural biology [Acta Crystallogr D Struct Biol] 2023 Sep 01; Vol. 79 (Pt 9), pp. 837-856. Date of Electronic Publication: 2023 Aug 10.
DOI: 10.1107/S205979832300582X
Abstrakt: Due to the structural complexity of proteins, their corresponding crystal arrangements generally contain a significant amount of solvent-occupied space. These areas allow a certain degree of intracrystalline protein flexibility and mobility of solutes. Therefore, knowledge of the geometry of solvent-filled channels and cavities is essential whenever the dynamics inside a crystal are of interest. Especially in soaking experiments for structure-based drug design, ligands must be able to traverse the crystal solvent channels and reach the corresponding binding pockets. Unsuccessful screenings are sometimes attributed to the geometry of the crystal packing, but the underlying causes are often difficult to understand. This work presents LifeSoaks, a novel tool for analyzing and visualizing solvent channels in protein crystals. LifeSoaks uses a Voronoi diagram-based periodic channel representation which can be efficiently computed. The size and location of channel bottlenecks, which might hinder molecular diffusion, can be directly derived from this representation. This work presents the calculated bottleneck radii for all crystal structures in the PDB and the analysis of a new, hand-curated data set of structures obtained by soaking experiments. The results indicate that the consideration of bottleneck radii and the visual inspection of channels are beneficial for planning soaking experiments.
(open access.)
Databáze: MEDLINE
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