Thermodynamic Proxies to Compensate for Biases in Drug Discovery Methods

We propose a framework with simple proxies to dissect the relative energy contributions responsible for standard drug discovery binding activity. We explore a rule of thumb using hydrogen-bond donors, hydrogen-bond acceptors and rotatable bonds as relative proxies for the thermodynamic terms. We apply this methodology to several datasets (e.g., multiple small molecules profiled against kinases, Mycobacterium tuberculosis (Mtb) high throughput...