One of the research lines of the Costanzi Research group focuses on the application of computational chemistry to the study of the interaction of chemicals with living organisms. We are particularly 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).

Chemicals and living organism. 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.

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 (X-ray structure by Kobilka et al. PDB ID: 4LDO).

Computational Chemistry. With these premises in mind, we conduct computational modeling 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: