Research

Folding pathways using mechanical force in single-molecules

RNA folding, which includes thermodynamic and kinetic folding, is one of the most important problems in biophysics. Emergence of new classes of RNAs with regulatory functions such as riboswitches, non-coding RNAs, small RNAs has further highlighted this unsolved problem. Furthermore, with emerging reports of new riboswitches it is evident that RNA molecules can adopt complex architecture to perform gene regulatory activities. One of the challenging issues is: How do these RNA molecules fold into unique structure? What is the sequence dependence on pathways of RNA folding? What is the role of small molecules and ligands? Several experimental methods such as X-ray crystallography, NMR spectroscopy, fluorescence techniques have been used to provide high quality time-averaged snap shots of the structural information during folding. We are addressing RNA folding problems by exerting mechanical forces to single RNA molecules using optical tweezers. Various methods including force ramp, constant force and force-jump techniques are used in conjunction with RNA biochemistry.