The Group's Research Projects include the following:

In this research, we aim to decipher the relation between biophysical parameters of protein-protein interactions and biological activity. We were intrigued by the complex network of a large number of interferon subtypes binding the same two cell surface receptors, but seemingly causing differential activation. We assume that this differential activation is related to distinct modes of receptor binding, which can be investigated using purified proteins in vitro. Therefore, we developed methods to express, purify, mutate and measure the interaction between the different pieces of the puzzle in vitro. This work resulted both in a structural and functional model of the system. Yet, the interferon system is complex and still far from being understood, which is part of our plan for the future. Click here for a detailed description of our work in this area.

The process of protein-protein interactions can be divided into two kinetic, physically different processes. The first is the association process, where two proteins located far away have to find each other in a short time and form a complex. This process is second order, and depends on the concentration of the two reactants. The second process is of the dissociation of the two proteins, to form monomers. This process is independent on the protein concentration, and thus is of first order. Both processes were thoroughly investigated in our laboratory. In the following part, is a description of what we learned concerning the biophysical basis of the binding process, and how it was applied for protein design of faster and tighter binding protein complexes using the computer program PARE. Click here for a detailed description of our work in this area.

Joel Sussman, Israel Silman, Yigal Burstein, and Gideon Schreiber are currently leading the structural proteomics effort at the Weizmann Institute. The aim of the new Israel Structural Proteomics Center (ISPC) is to conduct structural analyses of a large number of proteins in parallel, and to combine the expertise of researchers from different fields. The Center is expected to significantly advance basic knowledge in this vast realm of inquiry, which could lead to important biomedical applications. As part of this effort, Gideon Schreiber is responsible for the protein expression part of the project, as well as being a member pf the steering committee.

In the last couple of years we have started to explore the huge wells of structure and sequence information available in the database to obtain a better understanding of protein-protein interactions in general. Our main goals include: the development of an algorithm which will be able to identify protein binding sites on the surface of unbound proteins; improving on existing docking algorithms and analyze the importance of fast; and electrostatically assisted association between proteins in the proteome. Click here for a detailed description of our work in this area.

Protein complexes are stabilized by non-covalent interactions similar to those, which stabilize the folded conformation of a protein. Simple mutagenesis studies have failed to reveal the nature of the complex interactions in the interface. Here we describe a new method, based on multiple-mutant cycles, developed to decipher the complex, and cooperative nature of non-covalent interactions, which result in the formation of stable protein complexes. Click here for a detailed description of our work in this area.