Rappertk: a versatile engine for discrete restraint-based conformational sampling of macromolecules.
| Autor: | Gore SP; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA UK. swanand@cryst.bioc.cam.ac.uk, Karmali AM, Blundell TL |
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| Jazyk: | angličtina |
| Zdroj: | BMC structural biology [BMC Struct Biol] 2007 Mar 21; Vol. 7, pp. 13. Date of Electronic Publication: 2007 Mar 21. |
| DOI: | 10.1186/1472-6807-7-13 |
| Abstrakt: | Background: Macromolecular structures are modeled by conformational optimization within experimental and knowledge-based restraints. Discrete restraint-based sampling generates high-quality structures within these restraints and facilitates further refinement in a continuous all-atom energy landscape. This approach has been used successfully for protein loop modeling, comparative modeling and electron density fitting in X-ray crystallography. Results: Here we present a software toolkit (Rappertk) which generalizes discrete restraint-based sampling for use in structural biology. Modular design and multi-layered architecture enables Rappertk to sample conformations of any macromolecule at many levels of detail and within a variety of experimental restraints. Performance against a Calpha-tracing benchmark shows that the efficiency has not suffered despite the overhead required by this flexibility. We demonstrate the toolkit's capabilities by building high-quality beta-sheets and by introducing restraint-driven sampling. RNA sampling is demonstrated by rebuilding a protein-RNA interface. Ability to construct arbitrary ligands is used in sampling protein-ligand interfaces within electron density. Finally, secondary structure and shape information derived from EM are combined to generate multiple conformations of a protein consistent with the observed density. Conclusion: Through its modular design and ease of use, Rappertk enables exploration of a wide variety of interesting avenues in structural biology. This toolkit, with illustrative examples, is freely available to academic users from http://www-cryst.bioc.cam.ac.uk/~swanand/mysite/rtk/index.html. |
| Databáze: | MEDLINE |
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