研究领域

Biophysical Chemistry Chemical Biology Computational/Theoretical Chemistry Physical Chemistry Theoretical Biophysics

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. This research is funded by the NIH. 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) and CSAR (Community Structure-Activity Resource). MOAD continues to grow with the PDB, and CSAR is developed with depositions of protein-ligand data from the pubic and private sectors. Websites for CSAR are coming soon. MOAD is currently available online (www.BindingMOAD.org), 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. This research is funded by the NSF and NIH.

近期论文

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Katrina W. Lexa and Heather, A. Carlson. Improving protocols for protein mapping through proper comparison to crystallography data. J. Chem. Inf. Model., 2013, 53, 391-402. Ann E. Davidson, Fazeel M. Siddiqui, Michael A. Lopez, Peter Lunt, Heather A. Carlson, Brian E. Moore, Seth Love, Donald E. Born, Helen Roper, Anirban Majumdar, Suman Jayadev, Hunter R. Underhill, Corrine O. Smith, Maja von der Hagen, Angela Hubner, Philip Jardine, Andria Merrison, Elizabeth Curtis, Thomas Cullup, Heinz Jungbluth, Mary O. Cox, Thomas L. Winder, Hossam Abdel Salam, Jun Z. Li, Steven A. Moore, James J. Dowling. Novel deletion of lysine 7 expands the clinical, histopathological and genetic spectrum of TPM2-related myopathies. Brain, 2013, 136, 508-521. Nickolay A. Khazanov, Kelly L. Damm-Ganamet, Daniel X. Quang, Heather A. Carlson. Overcoming sequence misalignments with weighted structural superposition. Proteins, 2012, 80, 2523-2535. Richard D. Smith, Alaina L. Engdahl, James B. Dunbar, Jr., Heather A. Carlson. Biophysical limits of protein-ligand binding. J. Chem. Inf. Model., 2012, 27, 2098-2106. Katrina W. Lexa and Heather A. Carlson. Protein flexibility in docking and surface mapping. Q. Rev. Biophys., 2012, 45, 301-343. Heather A. Carlson and James B. Dunbar Jr. A call to arms: what you can do for computational drug discovery. J. Chem. Info. Model., 2011, 51, 2025-2025. Richard D. Smith, James B. Dunbar Jr, Peter M.-U. Ung, Emilio X. Esposito, Chao-Yie Yang, Shaomeng Wang, and Heather A. Carlson. CSAR Benchmark Exercise of 2010: Combined evaluation across all submitted scoring functions. J. Chem. Info. Model., 2011, 51, 2115-2131. James B. Dunbar Jr, Richard D. Smith, Chao-Yie Yang, Peter M.-U. Ung, Katrina W. Lexa, Nickolay A. Khazanov, Jeanne A. Stuckey, Shaomeng Wang, and Heather A. Carlson. CSAR Benchmark Exercise of 2010: Selection of the protein-ligand complexes. J. Chem. Info. Model., 2011, 51, 2036-2046. Katrina W. Lexa, and Heather A. Carlson. Binding to the Open Conformation of HIV-1 Protease. Prot. Struct. Func. Bioinf., 2011, 79, 2282-2290. Steven A. Spronk, and Heather A. Carlson. The Role of Tyrosine 71 in Modulating the Flap Conformations of BACE1. Prot. Struct. Func. Bioinf., 2011, 79, 2247-2259. Katrina W. Lexa, and Heather A. Carlson. Full protein flexibility is essential for proper hot-spot mapping. J. Am. Chem. Soc., 2011, 133, 200-202. Adam D. Schuyler, Heather A. Carlson, and Eva L. Feldman. Computational methods for identifying a layered allosteric regulatory mechanism for ALS-causing mutations of Cu-Zn superoxide dismutase 1. Prot. Struct. Func. Bioinf., 2011, 79, 417-427. Lyra Chang, Yoshinari Miyata, Peter M.-U. Ung, Eric B. Bertelsen, Thomas J. McQuade, Heather A. Carlson, Erik R.P. Zuiderweg, and Jason E. Gestwicki. Chemical screens against a reconstituted multi-protein complex: Myricetin blocks DnaJ regulation of DnaK through an allosteric mechanism. Chem. & Biol., 2010, 18, 210-221. Ashley A. Reinke, Peter M.-U. Ung, Jerome J. Quintero, Heather A. Carlson, and Jason E. Gestwicki. Chemical probes that selectively recognize the earliest Aβ oligomers in complex mixtures. J. Am. Chem. Soc., 2010, 132, 17655-17657. Lyra Chang, Andrea D. Thompson, Peter M.-U. Ung, Heather A. Carlson, and Jason E. Gestwicki. Mutagenesis reveals the complex relationships between ATPase rate and the chaperone activities of Escherichia coli heat shock protein 70 (Hsp70/DnaK). J. Biol. Chem., 2010, 285, 21282-21291. Susanne Wisén, Eric B. Bertelsen, Andrea D. Thompson, Srikanth Patury, Peter M.-U. Ung, Lyra Chang, Christopher G. Evans, Gladis M. Walter, Peter Wipf, Heather A. Carlson, Jeffrey L. Brodsky, Erik R.P. Zuiderweg, and Jason E. Gestwicki. Binding of a small molecule at a protein-protein interface regulates the chaperone activity of Hsp70-Hsp40. ACS Chem. Biol., 2010, 5, 611-622. Mark L. Benson, Richard D. Smith, Nickolay A. Khazanov, Heather A. Carlson, Brandon Dimcheff, and Peter Dresslar. Updating Binding MOAD – Data management and information workflow. New Math. Natur. Comput., 2010, 6, 49-56. Adam D. Schuyler, Heather A. Carlson, and Eva L. Feldman. Computational methods for predicting sites of functionally important dynamics. J. Phys. Chem. B, 2009, 113, 6613-6622. Katrina W. Lexa, Kelly L. Damm, Jerome J. Quintero, Jason E. Gestwicki, and Heather A. Carlson. Clarifying allosteric control of flap conformations in the 1TW7 crystal structure of HIV-1 protease. Proteins, 2009, 74, 872-880. Heather A. Carlson, Richard D. Smith, Nickolay A. Khazanov, Paul D. Kirchhoff, James B. Dunbar, and Mark L. Benson. Differences between high- and low-affinity complexes of enzymes and non-enzymes. J. Med. Chem., 2008, 51, 6432-6441.(Hightlighted in Current Opinion in Drug Discovery and Development [2009 12:1-15.]