Nucleic Acids Research, 2006, Vol. 34, No. 4 e29 doi:10.1093/nar/gnj031 Nucleic acid visualization with UCSF Chimera Gregory S. Couch, Donna K. Hendrix1 and Thomas E. Ferrin* Computer Graphics Laboratory, Department of Pharmaceutical Chemistry, University of California, 600 16th Street, San Francisco, CA 94143-2240, USA and 1Department of Plant and Microbial Biology, 111 Koshland Hall # 3102, University of California, Berkeley, CA 94720-3102, USA Received December 14, 2005; Revised and Accepted January 31, 2006 ABSTRACT With the increase in the number of large, 3D, high-resolution nucleic acid structures, particularly of the 30S and 50S ribosomal subunits and the intact bacterial ribosome, advancements in the visualiza- tion of nucleic acid structural features are essential. Large molecular structures are complicated and detailed, and one goal of visualization software is to allow the user to simplify the display of some features and accent others. We describe an extension to the UCSF Chimera molecular visualization system for the purpose of displaying and highlighting nucleic acid characteristics, including a new representation of sugar pucker, several options for abstraction of base geometries that emphasize stacking and base pairing, and an adaptation of the ribbon backbone to accommodate the nucleic acid backbone. Molecules are displayed and manipulated interact- ively, allowing the user to change the representations as desired for small molecules, proteins and nucleic acids. This software is available as part of the UCSF Chimera molecular visualization system and thus is integrated with a suite of existing tools for molecular graphics. INTRODUCTION There has been an enormous increase in the size and number of deposited structures of nucleic acids in recent years, including high-resolution X-ray crystal structures of two riboswitches (1,2), two ribonuclease P structures (3,4), several ribozymes (5,6) and structures of multiple macromolecular-assemblages that include nucleic acids, such as the 30S (7) and 50S (8,9) ribosomal subunits, as well as the intact ribosome (10), and the nucleosome core particle (11,12). This growth is reﬂected in the increase of nucleic acid structures available from the Nucleic Acid Database (NDB) (13) and structure-related databases, such as the Structural Classiﬁcation of RNA (SCOR) database (14), a classiﬁcation of 3D structural motifs, with larger structures having many more motifs than smaller structures. SCOR doubled in the number of structures char- acterized between 2002 and 2004, and simultaneously increased by nearly 20-fold in the number of structural features characterized, from 423 internal and hairpin loops in version 1.1 to 8270 in version 2.0.3 (15). The viewing of macromolecular structures is improved by the use of tools that highlight, or if needed, abstract the details, of molecular features. And while many visualization tools exist and representations are standardized for protein struc- tures, these tools are often inadequate for the structural fea- tures of nucleic acids. It is a challenge of visualization methods to display and emphasize key concepts and features without overwhelming the viewer and while maintaining the accuracy of the data. For proteins, abstractions exist such as stylized ribbon representations of alpha helices and beta sheets accent- ing the different secondary structures and displaying the dir- ection of the chain, and for displaying the backbone and side chains (16); however, these methods fall short for nucleic acids, where the structural features are quite different from proteins. Here, we present a new tool for nucleic acid visualization that highlights the features of nucleic acids. We present a new representation to emphasize sugar pucker, a modiﬁcation to the backbone ribbon for the nucleic acid backbone, and several options for displaying bases and their interactions, emphasizing base pairing and base stacking. MATERIALS AND METHODS UCSF Chimera (17) (henceforth referred to as ‘Chimera’) is a molecular graphics program designed to maximize interactive visualization and collaboration, that also allows users to easily write additional tools to extend its capabilities. Chimera is available free of charge to academic and non-proﬁt users and is available on a wide array of platforms, including Microsoft Windows, Apple OS X and Linux. The nucleic acid visualization features presented here are an extension to the basic Chimera visualization system, and are currently *To whom correspondence should be addressed. Tel: +1 415 476 2299; Fax: +1 415 502 1755; Email: tef@cgl.ucsf.edu The Author 2006. Published by Oxford University Press. All rights reserved. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org