The DNA conformational energy landscape: Sequencedependent conformational equilibria of duplex DNA

Karim M ElSawy* and Leo SD Caves

The free energy surfaces of duplex dinucleotide steps were mapped in a principal conformational subspace derived from crystal structure data on DNA duplex oligomers. The three dimensional subspace, spanned by collective degrees of freedom representing linear combinations of the Cartesian coordinates of the backbone and sugar atoms of both strands accounted for 77% of the total variance of the observed structural distribution. The features of the subspace free energy surface correspond well to the distribution of observed structures exhibiting a clear separation of A- and B-family classes. The sequence dependence of the relative A / B-form conformational equilibria was derived from the corresponding subspace free energy surfaces at physiological conditions. A B-philicity scale representing the mole fraction of the BI-form vs the A-family for the 10 unique dinucleotide steps revealed three classes of sequences: highly B-philic (GC/GC & CG/CG), B-philic (AC/GT, AA/TT, AT/AT, CA/TG, AG/CT & GG/CC) and A-philic (GA/TC & TA/TA). The high propensity of the TA/TA step to adopt the A-form conformation is in accord with single crystal X-ray diffraction data and has biological signifi cance in view of the frequent presence of the TATA sequence motif in transcriptional promoter regions.

Keywords:

Published on: May 28, 2020 Pages: 1-9

Full Text PDF Full Text HTML DOI: 10.17352/ojcps.000002
CrossMark Publons Harvard Library HOLLIS Search IT Semantic Scholar Get Citation Base Search Scilit OAI-PMH ResearchGate Academic Microsoft GrowKudos Universite de Paris UW Libraries SJSU King Library SJSU King Library NUS Library McGill DET KGL BIBLiOTEK JCU Discovery Universidad De Lima WorldCat VU on WorldCat