title: Structure, dynamics, and function of the hammerhead ribozyme in bulk water and at a clay mineral surface from replica exchange molecular dynamics.
abstract: Compared with proteins, the relationship between structure, dynamics, and function of RNA enzymes (known as ribozymes) is far less well understood, despite the fact that ribozymes are found in many organisms and are often conceived as "molecular fossils" of the first self-replicating molecules to have arisen on Earth. To investigate how ribozymal function is governed by structure and dynamics, we study the full hammerhead ribozyme in bulk water and in an aqueous clay mineral environment by computer simulation using replica-exchange molecular dynamics. Through extensive sampling of the major conformational states of the hammerhead ribozyme, we are able to show that the hammerhead manifests a free-energy landscape reminiscent of that which is well known in proteins, exhibiting a "funnel" topology that guides the ribozyme into its globally most stable conformation. The active-site geometry is found to be closely correlated to the tertiary structure of the ribozyme, thereby reconciling conflicts between previously proposed mechanisms for the self-scission of the hammerhead. The conformational analysis also accounts for the differences reported experimentally in the catalytic activity of the hammerhead ribozyme, which is reduced when interacting with clay minerals as compared with bulk water.
authors: Centre for Computational Science, Department of Chemistry, University College London , 20 Gordon Street, London WC1H 0AJ, United Kingdom.
authors: Jacob B
authors: JB
authors: Swadling
authors: David W
authors: DW
authors: Wright
authors: James L
authors: JL
authors: Suter
authors: Peter V
authors: PV
authors: Coveney
mesh_terms: D000538:Aluminum Silicates / Q000737:chemistry*; D000077215:Clay; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D010316:Particle Size; D016337:RNA, Catalytic / Q000737:chemistry* / Q000378:metabolism; D013499:Surface Properties; D014867:Water / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000538:Aluminum Silicates; D016337:RNA, Catalytic; D014867:Water; D000077215:Clay