Book of Abstracts: Albany 2007
June 19-23 2007
Molecular dynamics simulations of Hepatitis Delta Virus and Hairpin ribozymes: distinct strategies to use pockets of deep electrostatic potential minima
Ribozymes are catalytically competent examples of highly structured noncoding RNAs, which are ubiquitous in the processing and regulation of genetic information. We present data from extensive explicit water molecular dynamics simulations of Hepatitis Delta Virus (HDVr) and Hairpin (HrRz) ribozymes. The simulations provide interesting insights into structural dynamics of these molecules, including their hydration and ion binding properties. The HDVr possesses a catalytic pocket with a very deep minimum of electrostatic potential (ESP) and shows extensive interactions with divalent and monovalent ions. The simulations are rather consistent with C75 acting as general base in the catalysis, provided the transition state does not dramatically differ from the ground state seen in the x-ray structures. HrRz shows a different strategy in utilizing a negative ESP pocket. Its pocket appears to be protected from ion binding and, instead, a set of structural waters lining up in the pocket is exposed to the negative ESP. HrRz exhibits a coupled hydrogen bonding network that communicates dynamic structural rearrangements throughout the catalytic core in response to site-specific chemical modification. Trapped long-residency water molecules are critical for this network and only occasionally exchange with bulk solvent as they pass through a breathing interdomain base stack. These highly structured water molecules line up in a string that may potentially also be involved in specific base catalysis. Our observations suggest important, still underappreciated roles for specifically bound water molecules in the structural dynamics and function of noncoding RNAs.
References and Footnotes
1Institute of Biophysics,