title: Calculation of pKas in RNA: on the structural origins and functional roles of protonated nucleotides.
abstract: pK(a) calculations based on the Poisson-Boltzmann equation have been widely used to study proteins and, more recently, DNA. However, much less attention has been paid to the calculation of pK(a) shifts in RNA. There is accumulating evidence that protonated nucleotides can stabilize RNA structure and participate in enzyme catalysis within ribozymes. Here, we calculate the pK(a) shifts of nucleotides in RNA structures using numerical solutions to the Poisson-Boltzmann equation. We find that significant shifts are predicted for several nucleotides in two catalytic RNAs, the hairpin ribozyme and the hepatitis delta virus ribozyme, and that the shifts are likely to be related to their functions. We explore how different structural environments shift the pK(a)s of nucleotides from their solution values. RNA structures appear to use two basic strategies to shift pK(a)s: (a) the formation of compact structural motifs with structurally-conserved, electrostatic interactions; and (b) the arrangement of the phosphodiester backbone to focus negative electrostatic potential in specific regions.
authors.affiliation: Howard Hughes Medical Institute, Center for Computational Biology and Bioinformatics, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Tang
authors.forename: Emil
authors.initials: E
authors.lastname: Alexov
authors.forename: Anna Marie
authors.initials: AM
authors.lastname: Pyle
authors.forename: Barry
authors.initials: B
authors.lastname: Honig
mesh_terms: D002384:Catalysis; D003698:Hepatitis Delta Virus / Q000737:chemistry / Q000378:metabolism; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009711:Nucleotides / Q000737:chemistry* / Q000378:metabolism*; D016012:Poisson Distribution; D017433:Protein Structure, Secondary; D011522:Protons; D012313:RNA / Q000378:metabolism*; D016337:RNA, Catalytic / Q000737:chemistry / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D009711:Nucleotides; D011522:Protons; D016337:RNA, Catalytic; D012367:RNA, Viral; C418481:hairpin ribozyme; D012313:RNA