Mike May wrote an article to Bio-IT World about eHiTS Lightning and our efforts to accelerate docking on the Cell BE processor. There are more details about the topic in our white paper, and some earlier blog posts here and here. Some people argue that speed is not the most important issue for docking, accuracy is far more crucial. They fail to realize the fact, that speed is a factor that can enable us to use much finer pose sampling and more sophisticated scoring terms and still run at reasonable time frame. Think about it this way: it is well known that quantum chemistry based methods, e.g. free enegy perturbation (FEP) can provide the most accurate binding energy estimation, yet nobody has ever considered using such technique for scoring in docking or virtual screening, simply because it takes many CPU hours to compute the energy for a single ligand pose with FEP while a single docking run requires many thousands, possibly millions of poses to be scored. If SimBioSys as a software vendor would offer a docking software with FEP scoring that requires years of CPU time for a single docking run, nobody would buy such a product. But if we could do FEP-score based docking such that it runs in a few minutes per ligand that would be a “killer application”.
Previous releases of the eHiTS software have already reached pose accuracy and enrichment results beyond the competitors, now eHiTS Lightning wins the speed race while still delivering the same, superior accuracy. Currently, we are working on trading some of the speed advantage for even better accuracy by using improved pose generation and scoring techniques. You know Lipinski’s rule of 5 for drug-like molecules. My goal is to establish the Zsoldos rule of 1 for eHiTS Lightning docking for all drug-like ligands:
- Pose accuracy under 1A RMSD from X-ray
- Run-time under 1 minute per ligand
- Binding affinity estimation with under 1log unit error
Of course, the challenge is to do all three together. We can already reach the first 2 for most cases, the third one seems to be the hardest.