Molecular models of DNA

About: Molecular models of DNA is a research topic. Over the lifetime, 300 publications have been published within this topic receiving 16805 citations.

Structural deformations of the DNA double helix in the first stages of DNA transcription studied with a simple model

Abstract: A very simple model of DNA in biological media, consisting of electric charges related to the phosphate groups and to counterions immersed in structured media of constant permittivity, is introduced and tested with the study of a model for the first stages of the DNA transcription. This process is modeled into two steps involving three ‘states’: (1) the DNA system at the equilibrium, (2) the DNA with a small portion deprived of counterions, and (3) the DNA with a partial opening of the double helix in correspondence of the zone deprived of counterions. An extensive investigation involving as variable parameters the length of the DNA specimen (from 31 to 1511 base pairs), the amount of condensed counterion charge (from complete compensation to zero), and the geometrical parameters identifying the local opening has shown that the proposed transcription mechanism is reasonable, and that the DNA model considered here may fill a gap between accurate models including all the interactions—and employed at present for small fragments—and unstructured models addressed to inspect the behavior at the limit of infinite DNA length.

Simulations Meet Experiment to Reveal New Insights into DNA Intrinsic Mechanics.

Abstract: The accurate prediction of the structure and dynamics of DNA remains a major challenge in computational biology due to the dearth of precise experimental information on DNA free in solution and limitations in the DNA force-fields underpinning the simulations. A new generation of force-fields has been developed to better represent the sequence-dependent B-DNA intrinsic mechanics, in particular with respect to the BI ↔ BII backbone equilibrium, which is essential to understand the B-DNA properties. Here, the performance of MD simulations with the newly updated force-fields Parmbsc0eζOLI and CHARMM36 was tested against a large ensemble of recent NMR data collected on four DNA dodecamers involved in nucleosome positioning. We find impressive progress towards a coherent, realistic representation of B-DNA in solution, despite residual shortcomings. This improved representation allows new and deeper interpretation of the experimental observables, including regarding the behavior of facing phosphate groups in complementary dinucleotides, and their modulation by the sequence. It also provides the opportunity to extensively revisit and refine the coupling between backbone states and inter base pair parameters, which emerges as a common theme across all the complementary dinucleotides. In sum, the global agreement between simulations and experiment reveals new aspects of intrinsic DNA mechanics, a key component of DNA-protein recognition.

ADAPT: a molecular mechanics approach for studying the structural properties of long DNA sequences.

Abstract: We describe an original approach to determining sequence–structure relationships for DNA. This approach, termed ADAPT, combines all-atom molecular mechanics with a multicopy algorithm to build nucleotides that contain all four standard bases in variable proportions. These nucleotides enable us to search very rapidly for base sequences that energetically favor chosen types of DNA deformation or chosen DNA–protein or DNA–ligand interactions. Sequences satisfying the chosen criteria can be found by energy minimization, combinatorial sequence searching, or genome scanning, in a manner similar to the threading approaches developed for protein structure prediction. In the latter case, we are able to analyze roughly 2000 base pairs per second. Applications of the method to DNA allomorphic transitions, DNA deformation, and specific DNA interactions are presented. © 2001 John Wiley & Sons, Inc. Biopolymers (Nucleic Acid Sci) 56: 292–310, 2001

Probing DNA mechanical characteristics by dielectrophoresis

Abstract: Microfabricated electrode systems have recently become useful for immobilization and stretching biopolymers to precise locations in microfluidic devices. In this paper we discuss the modeling, fabrication and characterization of such a platform to investigate the elongation and orientation of different-sized deoxyribose nucleic acid (DNA) molecules, tethered onto aluminum electrodes, by a distributed force applied along the DNA backbone under the influence of high frequency non-uniform ac electric fields. The DNA molecules are elongated from a random coil into an extended conformation and orientated along the electric field lines as a result of the forces acting on the molecules during the application of the ac electric fields. Stable elongation is observed in the frequency range 0.1–1 MHz, with field strengths of 0.3–1.9 MV/m. Maximum elongation for two different DNA fragments, irrespective of size, is found for frequencies about 100 kHz. With a model that incorporates dielectrophoresis directly, we show that electric field experimental results can be used for detecting some characteristics of the DNA elasticity which manifest themselves clearly at higher extensions but cannot be observed at lower ones. The entropic elasticity and highly extensibility of DNA are all closely related to this account. By the elastic DNA model presented and by considering the base–stacking interactions between DNA adjacent nucleotide base pairs, we find an underlying scaling relation between the DNA extension and the applied voltage of the form 〈 δ 〉 ∼ V p − p 1 − 1.15 , which emphasizes the significance of the electric fields.