Computational Methods for Tertiary RNA Folding and Novel RNA Design

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Project Abstract (NSF 0727001)Computational Methods for Tertiary RNA Folding and Novel RNA DesignRecent discoveries have revealed RNA's wonderful capacity to form complex three-dimensional structures, as well as perform many molecular functions beyond storage of biological information. RNA's newly realized powers are being exploited in bioengineering and nanotechnology for design and application of biological sensors for detecting chemical compounds (for example, toxins), RNA enzymes for enabling faster chemical reactions, RNA switches for controlling protein synthesis in the cell, and RNA microarrays for monitoring gene expression. These advances in RNA science have relied mostly on experimental techniques (for example, X-ray crystallography). However, the systematic theoretical 3D structure determination and design approaches that have greatly benefited protein science are largely lacking for RNA. This void hampers the integration of experimental and theoretical tools required for advancing emerging RNA applications in bioengineering and nanotechnology. This research focuses on developing computational technologies for RNA 3D structure prediction and design. For RNA 3D structure prediction, the investigators study algorithmic development issues involving calculating and testing RNA statistical potentials, and developing/applying effective Monte Carlo conformational sampling algorithms coupled with the fragment assembly approach, a successful method for protein structure prediction. In particular, the investigators examine the role of multibody interactions in RNA 3D structure prediction. For RNA 3D design, the investigators focus on procedures for designing novel RNAs with tailored functions by a systematic computational approach. This work involves integrating RNA 2D/3D folding algorithms with advanced dynamics analysis tools (for example, QM/MM, transition path sampling) to screen and elucidate the structural, dynamical, and ligand-binding properties of designed RNAs. The computational tools for RNA 3D structure prediction and design resulting from the studies are being made available as a software package to the research community.