Computational Design of Novel Enzymes and Small Molecule Binding Proteins

Project Description

Starting September 2012, projects will focus on the computational design of novel enzymes and small molecule binding proteins. Through billions of years of evolution, nature has come up with enzyme catalysts with exquisitely high and finely tuned efficiencies and selectivities. We will design new catalysts for natural and non-natural (not catalyzed by existing enzymes) reactions by mimicking the process of biological evolution on the computer and in the laboratory. Some questions that projects will attempt to answer are:

  1. How do new enzymatic activities arise from existing ones? Can we design an enzyme activity not found in nature into an existing enzyme?
  2. How do natural proteins signal that they have bound a small molecule ligand? Can we design molecular on-off switches?


Course Experience

Preferred (but not required): Biochemistry, Thermodynamics.


Current Undergraduate Researchers

Fahad Mohammad (to join in Sept 2012)


Publications with Undergraduate Co-authors

S. D. Khare, F. Ding, K. N. Gwanmesia, and N. V. Dokholyan, “Molecular origin of polyglutamine-mediated aggregation in neurodegenerative diseases” PLoS Comp. Biol., 1: e30 (2005).

S. Barton, R. Jacak, S. D. Khare, F. Ding, and N. V. Dokholyan, "The length dependence of the polyQ-mediated protein aggregation" J. Biol. Chem., 282: 25487-25492 (2007).

(undergraduate author in bold)

Research Area: