RESISTOR: A New OSPREY Module to Predict Resistance Mutations

[摘要] Computational, in silico prediction of resistance-conferring escape mutations could accelerate the design of therapeutics less prone to resistance. This article describes how to use the Resistor algorithm to predict escape mutations. Resistor employs Pareto optimization on four resistance-conferring criteria—positive and negative design, mutational probability, and hotspot cardinality—to assign a Pareto rank to each prospective mutant. It also predicts the mechanism of resistance, that is, whether a mutant ablates binding to a drug, strengthens binding to the endogenous ligand, or a combination of these two factors, and provides structural models of the mutants. Resistor is part of the free and open-source computational protein design software OSPREY.

[学科分类] 生物科学（综合）

[关键词] cancer;mutation;OSPREY;Pareto;resistance;RESISTOR