This Week In Cheminformatics: Issue #025

BigSMILES canonicalization, Cleavage Rules Using SMIRKS Heuristics, EasyDock 1.3, and a long list of papers

Jun 14, 2026

Highlights

A Canonical Text Representation for Polymers via BigSMILES and Tree Automata

Handling stochastic polymer representations in databases just got significantly more manageable thanks to a new paper from the Olsen lab on BigSMILES canonicalization. BigSMILES successfully encodes the structural connectivity of complex polymer ensembles, but, its inherent string degeneracy makes routine graph-based searches computationally expensive. The authors present a robust algorithm that maps linear and branched BigSMILES strings onto tree automata state machines that recognize branch points. It then minimizes these branch points into unique graphs, and translates the transition rules back into human-readable, canonicalized strings. Fun read !

EasyDock 1.3: An Automated Pipeline for Molecular Docking

Minibaeva et al. present EasyDock 1.3 as a useful tool for large-scale virtual screening campaigns. What makes this release particularly relevant is its complete transition to an open-source ligand preparation pipeline, replacing commercial dependencies with tools like Uni-pKa and MolGpKa for thermodynamic-aware protonation state assignment. Crucially, this pipeline natively integrates PoseBusters and ProLIF for automated post-docking validation and protein-ligand interaction fingerprinting, storing the geometric pass/fail flags and interaction data directly in a SQLite database. I think I’m going to switch to this, goodbye DockingPie, you had a good run.

CRUSH—Cleavage Rules Using SMIRKS Heuristics: an enhanced molecular fragmentation algorithm

López-López et al. introduce CRUSH (Cleavage Rules Using SMIRKS Heuristics) as a comprehensive, chemistry-aware bond disconnection strategy. This method applies 33 curated SMIRKS based rules across all eligible bonds at each fragmentation step. The authors benchmarked CRUSH across five diverse datasets including natural products and macrocycles and demonstrated that it consistently shows smaller, Rule of Three-compliant fragments that cover regions of chemical space untouched by existing methods.