DNA Software, Inc., awarded an NIH SBIR fast track grant for the development of “Software for the Accurate de novo 3D Structure Prediction of RNA”
RNA-123TM Structural Biology Software
The discovery of new and interesting RNA sequences from genome sequencing projects, and the urgency to unravel their functions and develop new therapeutics, has led to a dramatic need for RNA three dimensional (3D) structural information. Current experimental methods for 3D structure determination of nucleic acids such as X-ray crystallography and NMR cannot keep pace with the daily discovery of sequences that need representative structures to be solved or modeled. Thus, there is a clear need for accurate 3D structure prediction tools that require only the primary sequence as input and can incorporate experimental constraint information when available. RNA-123™ has been developed specifically for this purpose with a major advantage of being automated, easy to use and also runs fast on a personal computer even when modeling large structures such as the ribosome. Additionally, the force field has been developed specifically for RNA which is a better approach than relying on protein prediction methodologies to predict RNA structure despite the significant differences between these two groups of molecules.
DNA Software, Inc. has developed a suite of software tools called RNA-123™ (RNA Primary–Secondary-Tertiary Structure) for RNA structural analysis, RNA homology modeling, and RNA de novo prediction. RNA-123™ has a unique force field specifically optimized for RNA. This tool has demonstrated success in homology modeling of large RNA-protein complexes such as the 70S ribosomal structure of Pseudomonas aeruginosa.
Validation studies have been carried out to assess the automated homology modeling approach. As an example, the Thermus Thermophilus 30S ribosomal subunit was modeled using the published 30S crystal structures of the E. coli ribosome (PDB ID 2AVY) as a template and vice versa. This study has resulted low-energy structural models of near crystal structure quality, (RMSDs between predicted models and published crystal structures is < 4 Å) with correctly predicted base pairing, stacking and tertiary interactions. Additionally, the robustness of the tool has been demonstrated through a validation study utilizing a diverse set of RNA targets such as riboswitches, ribozymes, and ribosomes.
Summary of Functionalities:
- RNA Homology modeling
- RNA De novo structure prediction
- Structure-based sequence alignment –(SBSA)
- RNA secondary and tertiary structure visualization GUI
- Tertiary structure editing, structure optimization and analysis
- Secondary structure folding
RNA-123™ will be available by licensing to academic (with discounted pricing), non-profit, and industrial users. RNA-123™ is written in C++ and currently runs on Windows operating systems with implementations for LINUX and web access under development. RNA-123™ is scheduled for release in the spring of 2011.