For decades, computer-aided drug design (CADD) has held the promise of greatly accelerating drug discovery and bringing much needed pharmacotherapeutic solutions to patients and medical professionals. CADD practitioners like to point to success stories such as the development of raltegravir -an HIV integrase inhibitor -and doramapimod -a highly potent kinase inhibitor -where modeling and simulation have been instrumental in bringing about new therapeutic agents. In the case of raltegravir, all-atom molecular dynamics (MD) simulations revealed a cryptic trench in HIV integrase and led to the discovery of a new class of antiretrovirals -the integrase inhibitors . Similarly, explicit solvent MD simulations revealed a 10 Å shift of the F169 side chain of p38 MAP kinase, exposing a cryptic pocket in the presence of BIRB 796 -a novel ligand, later named doramapimod -which was evaluated by Boehringer Ingelheim in clinical trials for the treatment of inflammatory diseases . As it samples and explores different conformational states, molecular dynamics is particularly well suited to identifying cryptic pockets which remain occluded in many crystal structures . While raltegravir and doramapimod are excellent examples of molecular modeling and dynamics delivering new and actionable knowledge that leads to new drugs or drug-like molecules, one only has to remember that there are hundreds of types of cancer accounting for millions of deaths yearly to realize there remains much to be desired. Indeed, while the rapid turnaround in silico hit discovery provides and the unraveling of biomolecular association mechanisms are certainly beneficial to drug design and discovery, there is no shortage of diseases and malignancies in need of new vaccines and treatments. The lack of vaccines for malaria and hepatitis C , despite the decades of research, are two prominent examples. Moreover, even in certain cancers where there are therapeutic options available, such as pancreatic cancer, the survival rate is still very low , further exacerbating the need for new antineoplastic molecules .