HomePage

Costanzi Research - Homepage
The Costanzi Research Group
http://costanziresearch.blogspot.com
Led by Dr. Stefano Costanzi and based at the Department of Chemistry of American University , the Costanzi Research Group focuses on two main research lines. The first one, which is the object of this website, revolves around the application of computational chemistry to the study of the interactions of chemicals with living organisms. The second one revolves around policy analysis and the conceptualization of solutions to counter the proliferation of chemical weapons - see the Costanzi Report.

Biologically active molecules. Biologically active molecules are naturally occurring or synthetic chemicals that interact with leaving organisms affecting them in either a positive (e.g. pharmaceutivals) or negative manner(e.g. chemical warfare agents or toxins).

Examples of biologically active molecules.
Adrenaline, the fight or flight reaction hormone; doxepin, an antidepressant prescription drug; cocaine, a drug of abuse; sarin, a nerve agent used as a chemical weapon; aflatoxin B1, a mycotoxin.

The great majority of biologically active molecules exert their actions by binding to specific structures located in their target cells - quoting German immunologist and Nobel Prize winner Paul Ehrlich, “corpora non agunt nisi ligata”, or bodies are not active unless they bind to something.

Hence, to understand how biologically molecules chemicals regulate and alter physiological functions, discover new biologically active molecules, or disrupt the effect of those that are harmful, it is of fundamental importance to study the way these compounds interact with their biological targets.

     
Photo: Paul Ehrlich (1854-1915), Wikipedia

The great majority of biologically active molecules exert their actions by binding to specific structures located in their target cells - quoting German immunologist and Nobel Prize winner Paul Ehrlich, “corpora non agunt nisi ligata”, or bodies are not active unless they bind to something.


Photo: Paul Ehrlich (1854-1915), Wikipedia

Hence, to understand how biologically molecules chemicals regulate and alter physiological functions, discover new biologically active molecules, or disrupt the effect of those that are harmful, it is of fundamental importance to study the way these compounds interact with their biological targets.

An example of a biologically active compound bound to its biological target: adrenaline binds to one of its receptors to activate the fight of flight reaction. More notes on the figure...


With these premises in mind, we conduct computational research to produce models that can explain and forecast:
  • the structure and the functioning of the cellular targets of biologically active molecules;
  • the nature and the strength of the interactions between the chemicals and their targets;
  • the molecular properties of biologically active molecules in relation to their activity profile.

To this extent, among several others, some of the computational techniques that we use in our research include:
  • Homology modeling, to build three-dimensional models of targets for which experimental structures are not available;
  • Molecular docking and virtual screening, to afford three-dimensional models of biologically active chemicals bound to their targets or screen thousands or millions of compounds to infer their likelihood of binding to a given target;
  • QSAR techniques, to correlate the physicochemical and topological properties of biologically active chemicals with their activity and yield predictive models for the design of new molecules.

We are interested in: a) the development, optimization and/or testing of computational research strategies; and b) the application of computational methodologies to solve specific, contingent problems, for instance the identification of chemicals that can modulate the activity of a given target of interest.

Among biological targets, we are particularly interested in G protein-coupled receptors (GPCRs).

Disclaimer. The content of this website expresses solely the views of the writer, which should not be construed as the views of any present or past employer.