PROLIX: rapid mining of protein-ligand interactions in large crystal structure databases

Journal of Chemical Information and Modeling
Martin WeiselRama Kondru

Abstract

A central problem in structure-based drug design is understanding protein-ligand interactions quantitatively and qualitatively. Several recent studies have highlighted from a qualitative perspective the nature of these interactions and their utility in drug discovery. However, a common limitation is a lack of adequate tools to mine these interactions comprehensively, since exhaustive searches of the protein data bank are time-consuming and difficult to perform. Consequently, fundamental questions remain unanswered: How unique or how common are the protein-ligand interactions observed in a given drug design project when compared to all complexed structures in the protein data bank? Which interaction patterns might explain the affinity of a tool compound toward unwanted targets? To answer these questions and to enable the systematic and comprehensive study of protein-ligand interactions, we introduce PROLIX (Protein Ligand Interaction Explorer), a tool that uses sophisticated fingerprint representations of protein-ligand interaction patterns for rapid data mining in large crystal structure databases. Our implementation strategy pursues a branch-and-bound technique that enables mining against thousands of complexes within a few se...Continue Reading

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Citations

Jan 19, 2013·Journal of Chemical Information and Modeling·Tuomo KalliokoskiAnna Vulpetti
Feb 26, 2013·Journal of Chemical Information and Modeling·Jérémy DesaphyDidier Rognan
Jul 23, 2013·Database : the Journal of Biological Databases and Curation·Adrian M Schreyer, Tom L Blundell
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Jan 28, 2017·Journal of Chemical Information and Modeling·Therese InhesterMatthias Rarey
Dec 1, 2013·Molecular Informatics·D Rognan
Jan 16, 2021·Journal of Biomolecular Structure & Dynamics·Debajeet GhoshRajesh Gacche
May 6, 2021·Nucleic Acids Research·Melissa F AdasmeMichael Schroeder
Aug 8, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bing BaiShuguang Yuan

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