Conformational Space of Nucleic Acids Bohdan Schneider Institute of Organic Chemistry and Biochemistry AS Czech Republic Supported by the grant LC512 from MŠ MT to the Center for Biomolecules and Complex Molecular Systems

Motivation  Nucleic acids have key biological functions  Folding realized via the backbone conformational variability  Function might be connected to fold

Data for the Analysis  NA backbone analyzed across the NDB archive:  DNA: About Eight thousand nt units  RNA: About Four thousand nt units

Analysis of Multidimensional Space  One nucleotide has 7 torsion angles ~ 7D conformational space  Largest variability at the phosphodiester link  A minimal unit for analysis >>ribose-to-ribose<<  Analyze several 3D slices through the 14D space

Approaches to Data Analysis  Duarte et al.  probably oversimplified NA conformational space, six torsions  two pseudotorsions 1. Murray et al. (Richardson’s lab., Duke U.)  apply data quality filter  analyze ribose-to-ribose “suite” with 6 torsions in two 3D distributions 2. Schneider et al.  powerful averaging of noisy distributions by FT  simple lexicographical clustering  Combination of 1. and 2. will improve definition of RNA conformational families

Averaging of 3D distributions by Fourier averaging Point distributionPseudoelectron representation

Fourier transforms of 3D torsion distributions  Calculated ~fifteen 3D maps  In all, fit peaks, assign residues to peaks  Sorted residues by lexicographical clustering:  6 primary maps for clustering  5 to monitor quality of proposed clusters  6 more or less ignored in the analysis

3'RESIDUE 5'  GA1448UH3H1B.??D.?? GU1985UH3H1G.??D.?? AC2021CH3H1B.??D.?? UA327GH2 AAG1??C. UA397UH2 A3??F.?? AG873UH2 AAG1??C. CC1651CH2 AA?? UC558CH1J.AA?? AB GG680GH1J.AAG2D.AB AG775CH1J.A1??D.AB GU374GH1 AAG2D.AB CA449GH1 A4??D.?? Clustering by Peak Names

Protocol  Select structural data  Fourier-transform 3D distributions of torsions  Localize peak positions in all maps  Fit and name peaks  Name di-nts by nearby peaks  Cluster di-nts by their names  Check clusters by overlap in real 3D  Well overlapping dints form conformational family

DNA is conformationally compact

RNA is conformationally diverse