Decoding the effect of temperatures on conformational stability and order of the ligand unbound thermo-sensing adenine riboswitch using molecular dynamics simulation

The structure-function relationship of the riboswitch is governed mainly by two factors, ligand binding and temperature. Most of the experimental studies shed light on structural dynamics and gene regulation function of Adenine riboswitch from the aspect of ligand instead of temperature. Two unliganded Adenine riboswitch conformations (apoA and apoB) from the thermophile Vibrio vulnificus draw particular attention to the Biophysics research community due to their diverse and polymorphic structures. Ligand-free apoB Adenine riboswitch conformation is not able to interact with the ligand whereas ligand-free apoA Adenine riboswitch conformation adopts ligand-receptive form. The interconversion between apoA and apoB conformation is temperature-dependent and thermodynamically controlled. Therefore Adenine riboswitch is called a temperature sensing RNA. The molecular mechanism underlying the thermosensitivity of ligand free Adenine riboswitch is not well known. Hence it is essential to explore temperature-induced conformational dynamics of unliganded Adenine riboswitch. In this research work I make an attempt to examine conformational stability and order of apoA with respect to apoB Adenine riboswitch aptamer using conformational thermodynamics derived from all-atom molecular dynamics trajectories in the temperature range 283K-400K. The changes in conformational free energy and entropy of conformational degrees of freedom like pseudo-torsion angle and {theta} are computed. RMSD, RMSF, RG, principal component analysis, hydrogen bonding interaction, and conformational thermodynamics data demonstrate that conformational stability and order of apoA with respect to apoB adenine riboswitch conformation is significant at 293K and 303K. The temperatures corresponding to the conformational order and stability of apoA adenine riboswitch with respect to apoB adenine riboswitch whole aptamer are shown in descending order 293K[~]303K> 313K[~]283K>373K>323K. The topological and conformational changes related to hydrogen bonding reorganization occur mostly at temperature 323K and 400K. Ligand unbound adenine riboswitch is sensitive to heat and may be inactivated at temperatures 323K and 400K. HighlightsO_LIMolecular Dynamics Simulation of ligand unbound two different conformations of adenine riboswitch with the same sequence at different temperatures are performed. C_LIO_LIAt low temperatures (293K and 303K) the conformational stability of apoA is more pronounced compared to apoB adenine riboswitch. C_LIO_LIThermal stability of apoA compared to apoB adenine riboswitch is the least at 323K temperature. C_LIO_LIAt higher temperature (373K) and lower temperature (283K) apoA adenine riboswitch exerts moderate conformational stability. C_LIO_LIThe nucleotides from stem2 and junction (J1/2, J2/3) regions of adenine riboswitch contribute the most to the conformational stability and order. C_LI