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

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

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

5. 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

6. 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

7. Averaging of 3D distributions by Fourier averaging Point distributionPseudoelectron representation

8. 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

12. 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

13. 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

14. DNA is conformationally compact

15. RNA is conformationally diverse