faculty

Associate Professor of Chemistry
John G. Searle Assistant Professor of Medicinal Chemistry (College of Pharmacy)
Ph.D., Yale University

Computational Chemistry, Theoretical Biophysics

Phone: (734) 615-6841
E-mail: carlsonh@umich.edu

Group Home Page

In my research, quantum mechanics, statistical mechanics, molecular mechanics, and database mining techniques are used to investigate chemical and enzymatic systems of biomedical importance. Structure-function relationships and > enzymatic regulation often result from subtle details at the atomic level; this detail is beyond the scope of current experimental methods for biological systems. Understanding enzymatic control allows us to explain the mechanism of disease and suggest routes for inhibition. Our research focuses primarily on protein-ligand recognition, protein flexibility, and new methods for computer-aided drug discovery.

One of the major projects in my lab is the development of a method for incorporating protein flexibility into the drug design process. A particular breakthrough with this method is that unbound, apo protein structures can be successfully used in drug design. If the community does not need to wait for ligand-bound crystal structures, we can tackle important systems years earlier than previously possible.

The other major project in the lab is the continued curration of the largest database of protein-ligand complexes: Binding MOAD (Mother of All Databases). This dataset continues to grow with the PDB. It is available online, and we continue to develop web-based tools that allow other users to pull information from our dataset. The patterns within this dataset allow us to better understand the molecular recognition behind ligand-binding events.

AWARDS

• Wiley International Journal of Quantum Chemistry Young Investigator Award (2006)
• College of Pharmacy's Student Appreciation Award for Excellence in Teaching (2005)
• National Science Foundation Career Award for 2005
• 2002 Beckman Young Investigator Award

REPRESENTATIVE PUBLICATIONS

1. Liegi Hu, Mark L. Benson, Richard D. Smith, Michael G. Lerner, and Heather A. Carlson. Binding MOAD (Mother of All Databases). Prot. Struct. Func. Bioinformatics, submitted.
2. KL Meagher, HA Carlson. Incorporating protein flexibility in structure-based drug discovery: Using HIV-1 protease as a test case. J. Am. Chem. Soc. 2004, 126, 13276-13281. (Highlighted in Nature Rev Drug Discovery)
3. H Zhong, HA Carlson. Computational Studies and Peptidomimetic Design for the Human p53-MDM2 Complex. Prot. Struct. Func. Bioinformatics 2005, 58, 222-234.
4. KL Meagher, HA Carlson. Solvation influences flap collapse in HIV-1 protease. Prot. Struct. Func. Bioinformatics 2005, 58, 119-125.
5. HA Carlson. Protein flexibility and drug discovery: How to hit a moving target. Curr. Opin. Chem. Biol. 2002, 6, 447-452.