title: Theoretical studies of RNA catalysis: hybrid QM/MM methods and their comparison with MD and QM.
abstract: Hybrid QM/MM methods combine the rigor of quantum mechanical (QM) calculations with the low computational cost of empirical molecular mechanical (MM) treatment allowing to capture dynamic properties to probe critical atomistic details of enzyme reactions. Catalysis by RNA enzymes (ribozymes) has only recently begun to be addressed with QM/MM approaches and is thus still a field under development. This review surveys methodology as well as recent advances in QM/MM applications to RNA mechanisms, including those of the HDV, hairpin, and hammerhead ribozymes, as well as the ribosome. We compare and correlate QM/MM results with those from QM and/or molecular dynamics (MD) simulations, and discuss scope and limitations with a critical eye on current shortcomings in available methodologies and computer resources. We thus hope to foster mutual appreciation and facilitate collaboration between experimentalists and theorists to jointly advance our understanding of RNA catalysis at an atomistic level.
authors.affiliation: Department of Physical Chemistry, Faculty of Science, Palacky University Olomouc, Olomouc, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Banás
authors.forename: Petr
authors.initials: P
authors.lastname: Jurecka
authors.forename: Nils G
authors.initials: NG
authors.lastname: Walter
authors.forename: Jirí
authors.initials: J
authors.lastname: Sponer
authors.forename: Michal
authors.initials: M
authors.lastname: Otyepka
mesh_terms: D001703:Biophysics / Q000379:methods; D002384:Catalysis; D003198:Computer Simulation; D006801:Humans; D008274:Magnesium / Q000737:chemistry; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D010710:Phosphates / Q000737:chemistry; D010766:Phosphorylation; D011789:Quantum Theory; D012313:RNA / Q000737:chemistry*; D016337:RNA, Catalytic / Q000737:chemistry; D012367:RNA, Viral / Q000737:chemistry; D012270:Ribosomes / Q000737:chemistry; D012984:Software
chemical_list: D010710:Phosphates; D016337:RNA, Catalytic; D012367:RNA, Viral; C427204:hammerhead ribozyme; D012313:RNA; D008274:Magnesium