We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
The multi-copy simultaneous search methodology: a fundamental tool for structure-based drug design.
- Authors
Schubert, Christian R.; Stultz, Collin M.
- Abstract
Fragment-based ligand design approaches, such as the multi-copy simultaneous search (MCSS) methodology, have proven to be useful tools in the search for novel therapeutic compounds that bind pre-specified targets of known structure. MCSS offers a variety of advantages over more traditional high-throughput screening methods, and has been applied successfully to challenging targets. The methodology is quite general and can be used to construct functionality maps for proteins, DNA, and RNA. In this review, we describe the main aspects of the MCSS method and outline the general use of the methodology as a fundamental tool to guide the design of de novo lead compounds. We focus our discussion on the evaluation of MCSS results and the incorporation of protein flexibility into the methodology. In addition, we demonstrate on several specific examples how the information arising from the MCSS functionality maps has been successfully used to predict ligand binding to protein targets and RNA.
- Subjects
DRUG design; METHODOLOGY; RADIOLIGAND assay; DYE-ligand affinity chromatography; DNA
- Publication
Journal of Computer-Aided Molecular Design, 2009, Vol 23, Issue 8, p475
- ISSN
0920-654X
- Publication type
Article
- DOI
10.1007/s10822-009-9287-y