The mutations that result in acquired drug resistance are a primary cause of drug failure in targeted drug therapy. Therefore, understanding the resistance mechanism is an important step forward in designing more effective anti-resistant drugs. To this end, we use a GPU-driven molecular dynamics sampling strategy to calculate the binding free energy surfaces. We studied two FDA-approved drugs, Crizotinib and Ceritinib, which are first and second generation ALK-targeted inhibitors, respectively, for treating ALK-positive non-small cell lung cancer. By monitoring the details of atomic-level protein-drug interactions before and after acquired resistance, we gain intrinsic insights into the drug resistance mechanisms and offer strategies to overcome that drug resistance.<br/>

Revealing ALK-drug resistance mechanisms using GPU-driven molecular dynamics sampling

2019 Fall National Meeting

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