Mesoscopic modeling of DNA denaturation rates: Sequence dependence and experimental comparison

Abstract

Using rare event simulation techniques, we calculated DNA denaturation rate constants for a range of sequences and temperatures for the Peyrard-Bishop-Dauxois (PBD) model with two different parameter sets. We studied a larger variety of sequences compared to previous studies that only consider DNA homopolymers and DNA sequences containing an equal amount of weak AT-and strong GC-base pairs. Our results show that, contrary to previous findings, an even distribution of the strong GC-base pairs does not always result in the fastest possible denaturation. In addition, we applied an adaptation of the PBD model to study hairpin denaturation for which experimental data are available. This is the first quantitative study in which dynamical results from the mesoscopic PBD model have been compared with experiments. Our results show that present parameterized models, although giving good results regarding thermodynamic properties, overestimate denaturation rates by orders of magnitude. We believe that our dynamical approach is, therefore, an important tool for verifying DNA models and for developing next generation models that have higher predictive power than present ones. C 2015 AIP Publishing LLC. [http://dx

DNA terminal base pairs have weaker hydrogen bonds especially for AT under low salt concentration

“…19 This provides us with the means of reinterpreting existing experimental data and extract new information about hydrogen bonds and stacking interactions for oligonucleotides. [19][20][21][22] There is a growing interest in obtaining parameters for the PB model, for instance Dahlen and van Erp 23 recently investigated the parameter dependencies in the context of denaturation rates. One of the attractive properties of this model is that its Hamiltonian can be easily adapted to reflect a number of different experimental situations such as DNA overstretching 24 or to include solvent interactions.…”

Modeling of PCR: Kinetic Explanation for Short‐Chained Side Products

“…This approach was chosen to model the processes taking place during the annealing step because experimental measurements of the kinetics during this process are difficult, thus, only very few have been reported in literature. On the other hand, the modeled rate constants for annealing as well as melting tend to be in the nanosecond range and, thus, orders of magnitude faster than the other processes considered in this model . Therefore, the reactions associated to these have reached a steady state long before the other reactions involved in PCR.…”

“…On the other hand, the modeled rate constants for annealing as well as melting tend to be in the nanosecond range and, thus, orders of magnitude faster than the other processes considered in this model [11]. This approach was chosen to model the processes taking place during the annealing step because experimental measurements of the kinetics during this process are difficult, thus, only very few have been reported in literature.…”

“…A kinetic description of PCR was suggested by Mehra et al, who also considered reactions in the extension phase, e.g., the formation of enzyme-primer-ssDNA complexes or the addition of nucleotides to one of these [9]. [11,12]. Most processes were treated using mass-action kinetics, giving a system of ordinary differential equations to be solved.…”

“…These models usually focus on the reaction at the molecular level , or treat only single stages of the reaction, such as denaturation, e.g. , .…”