High-throughput Binding Affinity Calculations at Extreme Scales

Jumana Dakka, Matteo Turilli, David W Wright, Stefan J Zasada, Vivek Balasubramanian, Shunzhou Wan, Peter V Coveney and Shantenu Jha

PaperAbstract. Resistance to chemotherapy and molecularly targeted therapies is a major factor in limiting the effectiveness of cancer treatment. In many cases, resistance can be linked to genetic changes in target proteins, either pre-existing or evolutionarily selected during treatment. Key to overcoming this challenge is an understanding of the molecular determinants of drug binding. Using multi-stage pipelines of molecular simulations we can gain insights into the binding free energy and the residence time of a ligand, which can inform both stratified and personal treatment regimes and drug development. To support the scalable, adaptive and automated calculation of the binding free energy on high-performance computing resources, we introduce the High-throughput Binding Affinity Calculator (HTBAC). HTBAC uses a building block approach in order to attain both workflow flexibility and performance.