Drexel University Engineering Professor Develops Protein Computer Model to Advance Pharmaceutical Drug Designs

March 2, 2010 Researchers at Drexel University’s Drexel Engineering are developing a new computer-based method to study the links between structure and flexibility of proteins that can one day be used to help advance pharmaceutical design.

“Many important proteins are quite flexible, but trying to capture this flexibility when all one has is a static ‘snapshot’ provided by, say, X-ray crystallography, has been a long-standing problem in structural biology. This technology expands the capabilities of standard all-atom molecular dynamics simulations to handle the long time-scales needed to observe protein motions. This enables us to postulate undiscovered protein structures which might actually be better targets for drug design than the crystal structures normally used,” said Dr. Cameron Abrams, associate professor of chemical and biological engineering and lead researcher on the project. 

The computational method implements the theory of Temperature Accelerated Molecular Dynamics (TAMD) developed by Abrams’ collaborator, Dr. Eric Vanden-Eijnden, a mathematician at New York University’s Courant Institute. The two recently published the method in The Proceedings of the National Academy of Sciences [2010; 107:4961-4966]. In this publication, the two show how TAMD can first ‘blindly’ reproduce a known conformational change in the E. coli GroEL chaperonin, proving that the method can make accurate predictions. Second, they showed how the method can be used to generate new structures for a protein that the human immunodeficiency virus (HIV-1) uses to target cells for infection.  Several of these new structures are now undergoing tests for the design of novel anti-AIDS drugs.
  
Funding for this research was provided by the National Science Foundation and the Office of Naval Research