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Abstract
The evolutionary docking generation of high numbers of potentially novel anticoagulant rodenticides is described here. In particular, made-on-demand libraries were generated by randomly introducing small molecular variations into alphafold-modeled brodifacoum-rat VKORC1 binding-cavity. For evolution of the brodifacoum parent, criteria were mainly optimized to fit-dock the brodifacoum cavity. Libraries of specific brodifacoum-children were selected by pooling those predicting higher affinities (lower binding-scores) at various molecular weights. The selected brodifacoum-children were filtered for known toxicities, desirable high affinity to recently identified spanish resistance rat mutants and undesirable high affinities to human VKORC1. The flexible threshold-adjustable new chemotype brodifacoum-children libraries constitute an step forward towards further in silico fine-tuning to computationally reduce other possible unspecific off-target ecological impacts
Supplementary materials
Title
Library C containing 150 children with filters in Data Warrior dwar
Description
The Table shows a prove-of-concept example of the evolutionary docking results described in the paper methodology. The docking-score thresholds of < -100 were applied to retain higher-affinities to rat wild-type and spanish mutants and the same threshold was applied to skip higher-affinities to human VKORC1. Any other thresholds can be applied using the filters at the right of the table. The dwar filecan be opened at Data Warrior free access https://openmolecules.org/datawarrior/download.htm
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