Distributions of bubble lifetimes and bubble lengths in DNA

Bubble lifetimes in DNA gene promoters and their mutations affecting transcription

“…The parameters K n,n−1 of Eq. ( 2) are taking on sequence specific values (see 29,30 ) and they have been shown to accurately reproduce peculiar denaturation transition temperatures exhibited by homogeneous and periodic DNA oligonucleotides 30 .…”

“…Random initial conditions were implemented, having a fixed energy corresponding to a temperature of 310 K, and the equations of motion were evolved using a symplectic integrator, namely the symplectic Runge-Kutta-Nystrøm fourth order integration scheme SRKNb6 45 . The threshold values of y thr AT = 0.24 Å and y thr GC = 0.15 Å are used in order to consider openings of A-T and G-C base pairs respectively, which are derived through the characteristic lengths of the corresponding Morse potential and are also consistent with the requirement that 50% of the DNA chain is open at the melting transition 29 . The system is evolved for 10 ns to provide thorough thermalisation, and then base pair displacement data are recorded every picosecond for the next nanosecond.…”

“…From this displacement data, the bubble probabilities and lifetime distributions can be calculated (see Ref. 29 for the details of the procedure). Then average bubble lifetimes are computed from the corresponding lifetime distributions.…”

“…without any environmental factors or effects from the surroundings, depending only on constant-energy fluctuations in the framework of a microcanonical evolution) across the sequence of different promoters -a viral, a bacterial, and a very strong artificial promoter -as well as comparisons with a corresponding mutant in each case that is known to either reduce or enhance transcriptional activity. Following a recent study of bubble lifetime distributions 29 , we use the PBD model 10 of DNA with sequence-dependent stacking parameters 30 , to perform constant-energy simulations (complementing earlier works implementing Langevin dynamics 3,22,28 ), in order to more closely probe the internal characteristic times of double strand openings without having to impose artificial time scales through arbitrary friction coefficients.…”

Mesoscopic helical models for nucleic acids

“…ii) As mentioned in Section 2.1, the partition function of the PB (and PBD) model is customarily computed in Transfer Integral methods by applying periodic boundary conditions which amount to close the linear chain into a loop [50,130]. This procedure is however questionable in short chains due to the relevance of finite size effects.…”