TY  - JOUR
AU  - Reim, Thorben
AU  - Ehrt, Christiane
AU  - Graef, Joel
AU  - Guenther, Sebastian
AU  - Meents, Alke
AU  - Rarey, Matthias
TI  - SiteMine: Large‐scale Binding Site Similarity Searching in Protein Structure Databases
JO  - Archiv der Pharmazie
VL  - 357
IS  - 5
SN  - 0365-6233
CY  - Weinheim
PB  - Wiley-VCH
M1  - PUBDB-2024-01661
SP  - 2300661
PY  - 2024
AB  - Drug discovery and design challenges, such as drug repurposing, analyzing protein–ligand and protein–protein complexes, ligand promiscuity studies, or function prediction, can be addressed by protein binding site similarity analysis. Although numerous tools exist, they all have individual strengths and drawbacks with regard to run time, provision of structure superpositions, and applicability to diverse application domains. Here, we introduce SiteMine, an all-in-one database-driven, alignment-providing binding site similarity search tool to tackle the most pressing challenges of binding site comparison. The performance of SiteMine is evaluated on the ProSPECCTs benchmark, showing a promising performance on most of the data sets. The method performs convincingly regarding all quality criteria for reliable binding site comparison, offering a novel state-of-the-art approach for structure-based molecular design based on binding site comparisons. In a SiteMine showcase, we discuss the high structural similarity between cathepsin L and calpain 1 binding sites and give an outlook on the impact of this finding on structure-based drug design. SiteMine is available at https://uhh.de/naomi.
LB  - PUB:(DE-HGF)16
C6  - 38335311
UR  - <Go to ISI:>//WOS:001159743600001
DO  - DOI:10.1002/ardp.202300661
UR  - https://bib-pubdb1.desy.de/record/606867
ER  -