New NIH funding awarded to UCSF School of Pharmacy postdoctoral fellows in 2011

New research support awarded to the UCSF School of Pharmacy by the National Institutes of Health during the 2011 fiscal year included two on-going projects by postdoctoral fellows:

Improving computer programs to yield better drug candidates

Ryan Coleman, PhD

  • Post-doctoral fellow in the laboratory of Brian Shoichet, PhD
  • Awarded an NIH fellowship of $48,398 in fiscal 2011, with an additional $52,190 of support in 2012

Coleman

Ryan Coleman, PhD

Coleman’s research seeks to improve the predictive accuracy of molecular docking computer programs. The programs virtually screen and score small molecules (ligands) for the relative strength with which they bind to proteins, thus changing their activity (e.g., inhibiting those involved in disease processes). The technology, first developed at the UCSF School of Pharmacy, is the basis of much modern drug discovery.

Specifically, Coleman is examining computer-simulated bindings at increasing levels of detail to more efficiently determine the best scoring ligand-protein combination.

He is putting the refined technique to work by screening ligands for a key protein, called dopamine receptor D3. While the receptor has been targeted for decades by drugs that treat conditions such as schizophrenia and addiction, many of those medications bind to other protein receptors as well. Such off-target binding is the molecular basis of medication side effects.

Coleman’s efforts to improve docking may yield better ligands with fewer off-target effects.

Regulating an enzyme’s action

Adam Steeves, PhD

  • Postdoctoral fellow in the laboratory of Matt Jacobson, PhD, jointly advised by John Gross, PhD, and David Morgan, PhD
  • Awarded an NIH fellowship of $48,398 in fiscal 2011, with an additional $52,190 of support in 2012

Steeves

Adam Steeves, PhD

Steeves’ work analyzes a process called allostery. The enzymes in our bodies have active sites where they bind to other molecules and catalyze biochemical reactions. Enzymes also have allosteric sites where molecules can bind to them and alter their activity—activating or inhibiting it. Steeves is looking at how a “signal” from a binding event at an allosteric site causes a change at an active site.

As a model, he is examining how allostery works in ubiquitination. In this process a group of enzymes work together to tag unnecessary proteins in the cell with a protein called ubiquitin. Once tagged, the proteins are targeted for destruction. A key hand-off of ubiquitin from one enzyme to another during the tagging of the condemned protein is apparently allosterically activated.

Steeves’ work to better understand allostery should help to develop new drugs that target allosteric sites, thus allowing more specific effects. For example, different enzymes with similar active sites could be more precisely targeted via allostery.

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About the School: The UCSF School of Pharmacy aims to solve the most pressing health care problems and strives to ensure that each patient receives the safest, most effective treatments. Our discoveries seed the development of novel therapies, and our researchers consistently lead the nation in NIH funding. The School’s doctor of pharmacy (PharmD) degree program, with its unique emphasis on scientific thinking, prepares students to be critical thinkers and leaders in their field.