Reactivity-weighted covalent natural-product screening workflow

Abstract

Reproducible in silico workflow for prioritizing covalent natural-product candidates against falcipain-2 and falcipain-3: Michael-acceptor filtering, dual recognition and covalent docking, MM-GBSA, and a multi-descriptor DFT reactivity analysis. The package includes the warhead-filtering cascade, retrospective enrichment benchmarks for falcipain-2 and falcipain-3 (property-matched and warhead-matched decoy controls, bootstrap confidence intervals), docking-box and recognition-ablation robustness checks, pH sensitivity, the OPT1 covalent cascade, DFT reactivity data with population-scheme, basis-set, and ΔSCF cross-checks, covalent pose coordinates, regression tests, and checksums.