Computer-designed proteins recognize and bind small molecules

Posted by: on Sep 6, 2013 | No Comments

Tinberg-and-team-1Computer-designed proteins that can recognize and interact with small biological molecules are now a reality. Scientists have succeeded in creating a protein molecule that can be programmed to unite with three different steroids.

The achievement could have far wider ranging applications in medicine and other fields, according to the Protein Design Institute at the University of Washington.

“This is major step toward building proteins for use as biosensors or molecular sponges, or in synthetic biology — giving organisms new tools to perform a task,” said one of the lead researchers, Christine E. Tinberg, a postdoctoral fellow in biochemistry at the UW.

The approach they took appears in the Sept. 4 online issue of Nature. Tinberg and Sagar D. Khare headed the study under the direction of David Baker, UW professor of biochemistry and Howard Hughes Medical Institute investigator. Khare is currently an assistant professor at Rutgers University.

Their Nature paper is accompanied by a News & Views commentary, “Computational biology: A recipe for ligand binding proteins.” The commentator, Giovanna Ghirlanda of Arizona State University, wrote that the method developed “to design  proteins with desired recognition sites could  be revolutionary” because cell processes such as cell cross-talk, the production of gene products and the work of enzymes all depend on molecular recognition.

The scientific team overcame previously unsolved problems in building accurate protein-small molecule interfaces.  Earlier attempts struggled with discrepancies between the computer plans and the structures of the actual molecules.

In conducting the study, the researchers learned general principles for engineering small molecule-binding proteins with strong attraction energies. Their findings open up the possibility that binding proteins could be created for many medical, industrial and environmental uses.

In medical diagnostics, for example, a rationally programmed protein might detect biomolecules found only in a specific disease state, such as an early-stage cancer.  Other types of protein molecules might eventually be manufactured to treat an overdose or to block a poison. Remediation possibilities for these molecular workhorses could include trapping pollutants or capturing waste.

“By continually improving the methodology and with feedback from experimental results,” the researchers noted in their paper, “computational protein design should provide an increasingly powerful approach to creating small molecule receptors for synthetic biology, therapeutic scavengers for toxic compounds, and robust binding domains for diagnostic devices.”