Tools for integrated sequence-structure analysis with UCSF Chimera.
BACKGROUND
Comparing related structures and viewing the structures in the context of sequence alignments are important tasks in protein structure-function research. While many programs exist for individual aspects of such work, there is a need for interactive visualization tools that: (a) provide a deep integration of sequence and structure, far beyond mapping where a sequence region falls in the structure and vice versa; (b) facilitate changing data of one type based on the other (for example, using only sequence-conserved residues to match structures, or adjusting a sequence alignment based on spatial fit); (c) can be used with a researcher's own data, including arbitrary sequence alignments and annotations, closely or distantly related sets of proteins, etc.; and (d) interoperate with each other and with a full complement of molecular graphics features. We describe enhancements to UCSF Chimera to achieve these goals.


RESULTS
The molecular graphics program UCSF Chimera includes a suite of tools for interactive analyses of sequences and structures. Structures automatically associate with sequences in imported alignments, allowing many kinds of crosstalk. A novel method is provided to superimpose structures in the absence of a pre-existing sequence alignment. The method uses both sequence and secondary structure, and can match even structures with very low sequence identity. Another tool constructs structure-based sequence alignments from superpositions of two or more proteins. Chimera is designed to be extensible, and mechanisms for incorporating user-specific data without Chimera code development are also provided.


CONCLUSIONS
The tools described here apply to many problems involving comparison and analysis of protein structures and their sequences. Chimera includes complete documentation and is intended for use by a wide range of scientists, not just those in the computational disciplines. UCSF Chimera is free for non-commercial use and is available for Microsoft Windows, Apple Mac OS X, Linux, and other platforms from http://www.cgl.ucsf.edu/chimera.
Meng
Elaine C
EC
Computer Graphics Laboratory, University of California San Francisco, 600 16th Street, San Francisco, CA 94143-2440, USA. meng@cgl.ucsf.edu
Pettersen
Eric F
EF
Couch
Gregory S
GS
Huang
Conrad C
CC
Ferrin
Thomas E
TE
D003196:Computer Graphics; D003198:Computer Simulation; D003628:Database Management Systems; D030562:Databases, Protein; D008956:Models, Chemical; D008958:Models, Molecular; D010363:Pattern Recognition, Automated / Q000379:methods; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000648:ultrastructure; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D012984:Software; D013329:Structure-Activity Relationship; D018511:Systems Integration; D014584:User-Computer Interface
D011506:Proteins