title: Mini-review: computational structure-based design of inhibitors that target protein surfaces.
abstract: Finding drugs that inhibit protein-protein interactions is usually difficult. While computer-aided design is used widely to facilitate the drug discovery process for protein targets with well-defined binding pockets, its application to the design of inhibitors targeting a protein surface is very limited. In this mini-review we address two aspects of this issue: firstly, we overview the current state of design methodology for inhibitors specifically targeting protein surfaces, and secondly, we briefly outline recent advances in computational methods for structure-based drug design. These methods are closely related to protein docking and protein recognition, the difference being that in ligand design, ligands are built on a fragment-by-fragment basis. A novel scheme of computational combinatorial ligand design developed for the design of inhibitors that interfere with protein-protein interaction is described in detail. Current applications and limitations of this methodology, as well as its future prospects, are discussed.
authors.affiliation: Molecular Modelling Laboratory, Ludwig Institute for Cancer Research, PO Box 2008, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia. Jun.Zeng@ludwig.edu.au
authors.forename: J
authors.initials: J
authors.lastname: Zeng
mesh_terms: D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D005544:Forecasting; D007136:Immunoglobulins / Q000187:drug effects; D008024:Ligands; D008956:Models, Chemical; D011506:Proteins / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D018909:src Homology Domains
chemical_list: D007136:Immunoglobulins; D008024:Ligands; D011506:Proteins