Flexibility of the B-DNA backbone: effects of local and neighbouring sequences on pyrimidine-purine steps

Abstract

The structurally correlated dihedral angles epsilon and zeta are known for their large variability within the B-DNA backbone. We have used molecular modelling to study both energetic and mechanical features of these variations which can produce BI/BII transitions. Calculations were carried out on DNA oligomers containing either YpR or RpY dinucleotides steps within various sequence environments. The results indicate that CpA and CpG steps favour the BI/BII transition more than TpA or any RpY step. The stacking energy and its intra- and inter-strand components explain these effects. Analysis of neighbouring base pairs reveals that BI/BII transitions of CpG and CpA are easiest within (Y)n(R)n sequences. These can also induce a large vibrational amplitude for TpA steps within the BI conformation.

MBO(N)D: A multibody method for long-time molecular dynamics simulations

“…This improvement in the unraveling and separation of the DNA strands is consistent with other evidence that suggests phosphate flexibility is important to the overall dynamics of DNA duplexes under equilibrium conditions. 91 The values of the rupture forces in Figure 12 are almost one order of magnitude higher than those observed by Konrad ) Nevertheless, the comparison between MBO(N)D and atomistic simulations is valid because both sets of runs were carried out under the same conditions. Our results are consistent with the experimental observation that the length of the DNA is increased by a factor of two in the stretched conformation over that of the unstretched conformation.…”

Dynamics of DNA: BIand BIIPhosphate Backbone Transitions

“…The DNA structure of the DrewDickerson dodecamer has been thoroughly investigated by means of X-ray crystal structure, NMR, and MD simulations. We constructed a canonical B-DNA 44 with the sequence d(CGCGAATTCGCG) 2 , using the program NUKIT. This structure was used as a reference and as the starting structure for our simulations.…”

“…The angle difference ( -) is close to -90°for B I and +90°for B II phosphates. 2,7,[9][10][11][12][13][14][15][16][17][18][19] With this study, we not only want to prove that the dynamics of the DNA backbone are fast and in the time scale of current MD simulations, but also that the overall distortions of the DNA structure that we introduced, corresponding to different starting structures for our MD simulation, are easily overcome during the course of the simulations and lead to trajectories that closely resemble canonical B-DNA. Hence, we are able to accurately investigate the interconversion of the phosphate substates that are important for interaction and recognition processes.…”

“…Hence, we are able to accurately investigate the interconversion of the phosphate substates that are important for interaction and recognition processes. For that purpose, we chose the Drew-Dickerson dodecamer d(CGCGAATTCGCG) 2 , as it has been under extensive study because of its biological relevance both structurally and theoretically. [20][21][22][23] This dodecamer contains the recognition site of the EcoRI restriction enzyme and serves as a well-studied reference system.…”

“…[24][25][26][27][28][29][30][31][32][33][34][35] In the present study, we are looking at the interconversion from one state to the other, starting from a restrained system. For that purpose, we performed several 10-ns MD simulations of the EcoRI DNA dodecamer d(CGC-GAATTCGCG) 2 , with all phosphates forced into the B I or B II state by restraints. These restraints were acting onto the and angles of the DNA backbone.…”