Zhang Initiative Research Unit

The complex biological functions of proteins are determined by their equally intricate three-dimensional structures. The correctly folded native structure is critical for the proper function of a protein in a cell. Small deviations from its native structure can often lead to malfunction of the protein and cause diseases. Our goal is to understand and modulate protein functions through computational studies of their structures. We are developing methods for protein structure prediction and applying design principles to create proteins with novel architectures, new biological functions or effective therapeutics. We are exploring new constraints to solve the X-ray crystallographic phase problem. We are also using the scaffold-based drug design method to discover new inhibitors for various drug targets.

Research Subjects

• Direct methods of phase retrieval in protein crystallography
• Density modification and phase improvement in X-ray crystallography
• Computational protein structure prediction
• Protein folding and design
• Scaffold-based drug design

Publications

1. Voet, A., Helsen, C., Zhang, K. Y. J., Claessens, F.:
   "The discovery of novel hAR receptor antagonist chemotypes using a combined pharmacophore screening procedure."
   ChemMedChem., DOI: 10.1002/cmdc.201200549 (2013)
2. Shrestha, R., Simoncini, D., Zhang, K. Y. J.:
   "Error-estimation-guided rebuilding of de novo models increases the success rate for ab initio phasing."
   Acta Cryst. D68., 1522-1534 (2012)
3. Kumar, A., Voet, A., Zhang, K. Y. J.:
   "Fragment based drug design: from experimental to computational approaches."
   Curr. Med. Chem., 19, 5128-5147 (2012)
4. Simoncini, D., Berenger, F., Shrestha, R., Zhang, K. Y. J.:
   "A probabilistic fragment-based protein structure prediction algorithm."
   PLoS ONE, 7, e38799, 1-11 (2012)
5. Voet, A., Zhang, K. Y. J.:
   "Pharmacophore modeling as a virtual screening tool for the discovery of small molecule protein-protein interaction inhibitors."
   Current Pharmaceutical Design, 18, 4586-4598 (2012)
6. Kumar, A., Zhang, K. Y. J.:
   "Computational Fragment-based Screening Using RosettaLigand: the SAMPL3 Challenge."
   J. Comput-Aided Mol. Des., 26, 603-616 (2012)
7. Berenger, F., Shrestha, R., Zhou, Y., Simoncini, D., Zhang, K. Y. J.:
   "Durandal: fast exact clustering of protein decoys."
   J. Compu. Chem., 33, 471-474 (2012)
8. Shrestha, R., Berenger F., Zhang, K. Y. J.:
   "Accelerating ab initio phasing with de novo models. "
   Acta Cryst. D67, 804-812 (2011)
9. Berenger F., Zhou Y., Shrestha, R., Zhang, K. Y. J.:
   "Entropy-accelerated exact clustering of protein decoys."
   Bioinformatics, 27, 939-945 (2011)
10. Berenger F., Coti C., Zhang K. Y. J.:
    "PAR: A PARallel And Distributed Job Crusher."
    Bioinformatics, 26, 2918-2919 (2010)