The objective of this research is to investigate induced fit phenomena involved in the formation of protein- RNA complexes using molecular dynamics (MD). Protein-RNA complexes are involved in all steps of mRNA processing and, as such, a complete understanding of the post-transcriptional regulation of gene expression is dependent upon knowledge of how protein-RNA recognition occurs. This investigation will be accomplished using several theoretical techniques. A study of the induced fit processes in protein-RNA complexes will be performed by investigating changes in structure and motions of complexes, uncomplexed forms, amino acid mutants and RNA base pair modifications of the U1A-stem loop 2 RNA system using all atom MD simulations. Contributions of the induced fit process to configurational entropy, binding affinity and specificity involved in U1A-RNA complexation will then be determined using free energy simulations and MMPBSA component analysis. Finally, using U1A-RNA as a prototype case, other theoretical means for studying protein-RNA complexes will be investigated, including MD in a PBSA solvent, hybrid QM/MM techniques, and variations on MD methodologies extended to larger time steps or reduced representations.
