This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.We have created a new extension to Chimera that provides visualization tools specific to nucleic acids. The available nucleic acid structural data hasincreased dramatically in recent years, primarily due to the solution of the ribosomal structures for T. thermophilus, H. marismortui, D. radiodurans, and E. coli. With this in mind, we are focusing on visualization methods that highlight the interactions and features that are unique to nucleic acids. This includes:1. Base stacking: Likely the most stabilizing interaction of a nucleic acid molecule, base stacking is a critical feature that we highlight by 'idealizing' individual base geometry, which is usually a very minor change to the base, and provide two ways of highlighting base visibility: by filling the base (and sugar, if one chooses), or by superposing three-dimensional rhomboids or ellipsoids. When seen, the bases appear as 'steps', making these critical stacking interactions, and (equally important) the disruption of stacking, immediately visible.2. Backbone geometry: The backbone of nucleic acids includes seven torsion angles, five more than in proteins, and thus backbone visualization methods for proteins do not fully capture the subtleties of nucleic acid structure. Thus, we are working toward adjusting the backbone ribbon visualization to optimize, and accurately reflect, the nucleic acid backbone.3. Base pairing and helices: Base pairing is the interaction between bases, famously described by Watson and Crick. Base pairs within helices are sometimes visualized as rungs on a ladder. We are examining similar types of visualization methods. This work is dependent upon the identification of proper base pairing and helical geometries, and thus requires the use of other software for this analysis (e.g., [3DNA] or [CURVES]) or that we create our own software for this purpose. This portion of the project is still under evaluation.4. Sugars: The DNA and RNA backbones contain a deoxyribose or ribose sugar. The sugar is a ring, and can take several different non-planarconformations. Our Chimera extension displays non-planar sugar conformation in a way that is easy to see, and also offers the user an opportunity to fill the sugar ring.While we strive to accent the uniquely important interactions of nucleic acids, we must pay close attention to existing standards, e.g. the standards set out by the Nomenclature Committee of the IUBMB [Standard]. It is key that our visualization methods follow existing standards, thus ensuring that the visual representation is correct and also much more likely to be accepted by the resesarch community.Our co-investigators are critical to this work. As structural biologists expert in nucleic acid and protein structure, they provide the necessary feedback to determine if these new visualization methods communicate the necessary information without obfuscation or distortion of the data. Dr. Nikolai Ulyanov is a structural biologist and an expert in RNA and DNA structure theory and determination with NMR. Dr. Donna Hendrix is a post-doctoral scholar currently working on the SCOR project. She is an expert in protein and RNA structural analysis and is the main tester for our new software. Lastly, Drs. Brenner and Holbrook are experienced researchers in the field.References:[3DNA] Xiang-Jun Lu & Wilma K. Olson (2003). '3DNA: a software package for the analysis, rebuilding and visualization of three-dimensionalnucleic acid structures', Nucl. Acids. Res., 31(17), 5108-5121.[CURVES] Biomol Struct Dyn. 1989 Feb;6(4):655-67. 'Defining the structure of irregular nucleic acids: conventions and principles.' Lavery R, Sklenar H.[Standard] Journal of Molecular Biology. Volume 313, Issue 1 , 12 October 2001, Pages 229-237 'A Standard Reference Frame for the Description of Nucleic Acid Base-pair Geometry'
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