It's a Perfect Protein Match

Biochemist, turned protein matchmaker, Dr. Gideon Schreiber of the Weizmann Institute of Science and doctoral student Tziki Seltzer, took their fate to heart. Working with colleagues at the Biological Chemistry Department, they developed a computer algorithm which calculates the rate at which two proteins associate, using it to fashion proteins with increased affinity - of a hundred times or more. Their achievement, recently appearing in Nature Structural Biology, holds much promise for the pharmaceutical and food industries, since protein complexes are fundamental to many life processes.

Protein affinity is defined by the rate at which two proteins associate with one another to form a complex, divided by the rate at which this complex dissociates. In order to improve protein affinity one can either intervene to reduce protein 'break-up' statistics, or alternatively, increase protein association rates. Dr. Schreiber chose the latter.

Since association rates are influenced by the protein's (genetically determined) design, the scientists used this relationship as their guiding principle - developing an algorithm capable of determining the genetic changes necessary to boost association rates.

Dr. Schreiber: 'A common approach to improving protein affinity is to create a large pool of mutations and discover the optimal complex through trial and error. However, the possibilities are often endless. Computer simulations are far more efficient in pinpointing potentially successful complexes.' Using the algorithm, the researchers increased the formation rate of a specific complex (b-lactamase protein and its inhibitor) by 250, as well as significantly enhancing its strength.

The new protein match-up system may lead to diverse medicinal applications based on increasing or inhibiting protein activity, as well as new diagnostic procedures, including antibody detection.

This research was funded by the Crown Endowment for Immunological Research, Chicago, Il. Dr. Gideon Schreiber holds the Dewey D. Stone and Harry Levine Career Development Chair in perpetuity.

The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel. Its 2,500 scientists, students and support staff are engaged in more than 1,000 research projects across the spectrum of contemporary science.