Hebrew University of Jerusale

Prof. Amiram Goldblum's

School of Pharmacy
Molecular Modeling and Drug Design Group

Ohad Givaty

MSc student

Designing new enzymes which are smaller than the original enzymes but retain the original activity

Project Description
The work is based on the assumption, that in many cases, if the structure and composition of the binding pocket is preserved, the activity will remain the same. The process by which I decrease the protein size is comprised of the following parts:
  1. Scoring the different sections in the protein according to their probability to affect the binding pocket if deleted. This process is based on :
    1. The level of interaction with the active site of each amino acid in the section
    2. The length of the gap created if the section is deleted
    3. The secondary structure elements in and around the section
  2. Section deletion. Creation of a few copies of the starting structure and deletion of a different section, which was scored as having low probabilities to affect the binding pocket if deleted, from each of them.
  • Gap closing. Running minimization processes, in which the binding pocket is kept frozen, on each structure. This is done in order to close the gaps and maintain protein like structures. The minimization is done using the Meshi program created in Dr Keasars lab in the Ben Gurion University.
  • Stabilizing the new structures. The new structures are stabilized by substituting the residues which have the worst energetic scores using the Rosetta protein design program. The Amino Acids of the binding pocket remain unchanged.
  • Eventually the most stable structure is chosen as the new starting structure and the process is repeated until I receive the desired size decrease or until the pocket of the decreased structure is no longer stable. To evaluate the stability of a structure I revised the Rosetta Reference Energy Function so that the scores will be independent of the protein length as well as being independent of its AA composition.

    2005 - now MSc, School of pharmacy, The Hebrew University Jerusalem. Part of the combined bioinformatics program
    1999 - 2002 BSc, computer science & bioinformatics, The Ben Gurion University

    email givatyo@pob.huji.ac.il
    Room 424


    Last Update : September 9, 2006 | Copyright ©, 2006, The Hebrew University of Jerusalem. All Rights Reserved.