Hi! I'm Mark, a research assistant professor at TTIC working on protein and drug design algorithms. I've been interested in protein design since the tenth grade, when I made a paper model of an enzyme (a ribonuclease) to see if I could figure out what mutations would make it specific to digest viral RNA. I realized soon that much more sophisticated techniques were needed, and as a graduate student in Bruce Donald's lab at Duke University, I began working on such techniques. The field has already made a lot of progress, and I think I've made some significant contributions (see below). But there is still a significant gap between the model of reality that we currently use in our designs, and the actual reality dictated by the laws of physics that determines how proteins and drugs behave in nature. Closing this gap would let us design molecules like an architect designs buildings—we will know ahead of time how they will work in real life. Builders building a skyscraper don't expect their first several tries to fall down, and we shouldn't have to expect that for drug design either. I think we can learn to design proteins and drugs in a similarly systematic way, even for fairly complicated functions.
Some algorithms I have developed toward this goal:
EPIC (Energy as Polynomials in Internal Coordinates)
DEEPer (Dead-End Elimination with Perturbations)
COMETS (Constrained Optimization of Multistate Energies by Tree Search)
LUTE (Local Unpruned Tuple Expansion)
CATS (Coordinates of Atoms by Taylor Series)
I have implemented all these algorithms as part of the OSPREY open-source protein design software package.