Journal of Computer-Aided Molecular Design

, Volume 20, Issue 2, pp 109–130

Development of small molecules designed to modulate protein–protein interactions

Authors

    • Laboratory of Computational Biology National Heart, Lung and Blood Institute, National Institutes of Health
  • Bernard R. Brooks
    • Laboratory of Computational Biology National Heart, Lung and Blood Institute, National Institutes of Health
  • Garland R. Marshall
    • Center for Computational Biology and Department of Biochemistry and Molecular BiophysicsWashington University
Article

DOI: 10.1007/s10822-006-9040-8

Cite this article as:
Che, Y., Brooks, B.R. & Marshall, G.R. J Comput Aided Mol Des (2006) 20: 109. doi:10.1007/s10822-006-9040-8

Summary

Protein–protein interactions are ubiquitous, essential to almost all known biological processes, and offer attractive opportunities for therapeutic intervention. Developing small molecules that modulate protein–protein interactions is challenging, owing to the large size of protein-complex interface, the lack of well-defined binding pockets, etc. We describe a general approach based on the “privileged-structure hypothesis” [Che, Ph.D. Thesis, Washington University, 2003] – that any organic templates capable of mimicking surfaces of protein-recognition motifs are potential privileged scaffolds as protein-complex antagonists – to address the challenges inherent in the discovery of small-molecule inhibitors of protein–protein interactions.

Keywords

conformational analysisdrug designpeptidomimeticsprotein–protein interactionprotein-surface mimeticsprivileged scaffoldtemplate design

Copyright information

© Springer Science+Business Media, Inc. 2006