10.1021/jp9076036.s001
Laura Riccardi
Phuong H. Nguyen
Gerhard Stock
Free-Energy Landscape of RNA Hairpins Constructed via Dihedral Angle Principal Component Analysis
2009
American Chemical Society
glycosidic torsional angle χ
dPCA
6 backbone dihedral angles
pseudorotational angle P
2 pseudotorsional angles η
RNA hairpins
RNA Hairpins Constructed
Dihedral Angle Principal Component AnalysisTo
Cartesian coordinates
dynamics simulation
SL
PCA
HIV
backbone dihedral angles
2 dihedral angles
UUCG
2009-12-31 00:00:00
article
https://acs.figshare.com/articles/Free_Energy_Landscape_of_RNA_Hairpins_Constructed_via_Dihedral_Angle_Principal_Component_Analysis/2803564
To systematically construct a low-dimensional free-energy landscape of RNA systems from a classical molecular dynamics simulation, various versions of the principal component analysis (PCA) are compared: the cPCA using the Cartesian coordinates of all atoms, the dPCA using the sine/cosine-transformed six backbone dihedral angles as well as the glycosidic torsional angle χ and the pseudorotational angle <i>P</i>, the aPCA which ignores the circularity of the 6 + 2 dihedral angles of the RNA, and the dPCA<sub>ηθ</sub>, which approximates the 6 backbone dihedral angles by 2 pseudotorsional angles η and θ. As representative examples, a 10-nucleotide UUCG hairpin and the 36-nucleotide segment SL1 of the Ψ site of HIV-1 are studied by classical molecular dynamics simulation, using the Amber all-atom force field and explicit solvent. It is shown that the conformational heterogeneity of the RNA hairpins can only be resolved by an angular PCA such as the dPCA but not by the cPCA using Cartesian coordinates. Apart from possible artifacts due to the coupling of overall and internal motion, this is because the details of hydrogen bonding and stacking interactions but also of global structural rearrangements of the RNA are better discriminated by dihedral angles. In line with recent experiments, it is found that the free energy landscape of RNA hairpins is quite rugged and contains various metastable conformational states which may serve as an intermediate for unfolding.