title: Free energy landscape and transition pathways from Watson-Crick to Hoogsteen base pairing in free duplex DNA.
abstract: Houghton (HG) base pairing plays a central role in the DNA binding of proteins and small ligands. Probing detailed transition mechanism from Watson-Crick (WC) to HG base pair (bp) formation in duplex DNAs is of fundamental importance in terms of revealing intrinsic functions of double helical DNAs beyond their sequence determined functions. We investigated a free energy landscape of a free B-DNA with an adenosine-thymine (A-T) rich sequence to probe its conformational transition pathways from WC to HG base pairing. The free energy landscape was computed with a state-of-art two-dimensional umbrella molecular dynamics simulation at the all-atom level. The present simulation showed that in an isolated duplex DNA, the spontaneous transition from WC to HG bp takes place via multiple pathways. Notably, base flipping into the major and minor grooves was found to play an important role in forming these multiple transition pathways. This finding suggests that naked B-DNA under normal conditions has an inherent ability to form HG bps via spontaneous base opening events.
authors.affiliation: Department of Chemistry and Institute of Functional Materials, Pusan National University, Busan 609-735, South Korea.
authors.forename: Changwon
authors.initials: C
authors.lastname: Yang
authors.affiliation: College of Pharmacy, Chosun University, Gwangju 501-759, South Korea.
authors.forename: Eunae
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Institute of Functional Materials, Pusan National University, Busan 609-735, South Korea ypak@pusan.ac.kr.
authors.forename: Youngshang
authors.initials: Y
authors.lastname: Pak
mesh_terms: D020856:AT Rich Sequence; D020029:Base Pairing; D059371:DNA, B-Form / Q000737:chemistry*; D056004:Molecular Dynamics Simulation
chemical_list: D059371:DNA, B-Form