Nucleic acid structures modeling

Ions are an important component in many chemical and biological systems. Nearly half of all proteins contain metal ions, and they play essential roles in many fundamental biological functions. Some metal ions are critical for both protein structure and function. In enzymes, ions can bind and orient the substrates through electrostatic interactions at the active sites, thus controlling catalytic reaction. Divalent ions are vital in nucleic acid structures. Modeling ion-water and ion-biomolecule interactions accurately is very important. 

Multistem nucleic acid structures [95], overlooked for a long time, are part of a great number of conserved biological nucleic acid sequences such as rRNAs. Three way junctions [33] are the simplest of all possible multistem nucleic acid structures. Model structures can be obtained when one mixes three mutually complementary nucleic acid single strands that form three double helical arms which meet at a common branch point (Figure 11, Table V). 

There are therefore four adjustable parameters per atom in the refinement (xy, yy, Zj, By). In the computer experiments we have carried out to test the assumptions of the nucleic acid refinement model we have generated sets of observed structure factors F (Q), from the Z-DNA molecular dynamics trajectories. The thermal averaging implicit in Equation III.3 is accomplished by averaging the atomic structure factors obtained from coordinate sets sampled along the molecular dynamics trajectories at each temperature ... 

Recently, Forsman developed a correlation-corrected PB model by introducing an effective potential between like-charge ions (Forsman, 2007). The effective potential at large ion-ion separation approaches the classical Coulomb potential and becomes a reduced effective repulsive Coulomb potential for small ion-ion separation. Such an effective potential represents liquid-like correlation behavior between the ions. For electric double layer with multivalent ions, the model makes improved predictions for the ion distribution and predicts an attractive force between two planes in the presence of multivalent ions (Forsman, 2007). However, for realistic nucleic acid structures, the model is computationally expensive. In addition, the ad hoc effective potential lacks validation for realistic nucleic acid structures. 

Macke T, Case DA (1998) Modeling unusual nucleic acid structures. In Leontes N, SantaLucia J Jr (eds) Molecular modeling of nucleic acids. American Chemical Society, Washington, D.C., pp 379-393... 

Cheatham TE, III (2004) Simulation and modeling of nucleic acid structure, dynamics and interactions. Curr. Opin. Struct. Biol. 14 (3) 360-367... 

Solvation plays a crucial role for the structure, dynamics and function of small molecules as well as for proteins and nucleic acids. When modeling solvation effects, especially for biomolecules, one often has to deal with large molecular systems and long timescales. Indeed, a proper account for solvation generally requires the inclusion of many solvent molecules, which leads to expanded system size and long simulation timescales required for capturing collective solvent response. 

The diffraction pattern to be expected for a helical structure was worked out in a theoretical study by William Cochran, Francis H. C. Crick, and Vladimir Vand using the a helix as a model. This work provided the basis for the interpretation of the diffraction patterns of proteins, and also led, unexpectedly, to an understanding of nucleic acid structure. This culminated in the determination of the three-dimensional structure of DNA by James D. Watson and Frances H. C. Crick from an X-ray diffraction photograph taken by Rosalind Franklin. 

In another approach, He et al. (He et al., 2013) proposed a 2-site per nucleotide (NARES-2P, nucleic acid united residue 2-point model) CG model where chain connectivity, excluded volume and base dipole interactions are sufficient to form helical DNA and RNA structures. This model was parametrized using a bottom-up strategy by employing a set of statistical potentials, derived from DNA and RNA structures from the Protein Data Bank, and the Boltzmann inversion method to reproduce the structural features. The base-base interactions were parametrized by fitting the potential of mean force to detailed all-atoms MD simulations using also the Boltzmann inversion approach. The respective potentials do not explicitly define the nucleic-acid structure, dynamics and thermod3mamics, but are derived as potentials of mean force. By detailed analysis of the different contribution to the Hamiltonian, the authors determined that the multipole-multipole interactions are the principal factor responsible for the formation of regular structures, such as the double helical structures. 

Empirical Approaches to Modeling Nucleic Acid Structure and Dynamics... 

This paper describes the development and initial applications of nab, a computer language for modeling biological macromolecules. It was developed to create atomic-level models of nucleic acid structures such as stem-loops, pseudoknots, multi-armed junctions and catalytic RNAs, and to investigate biological processes that involve nucleic acids, such as hybridization, branch migration at junctions, and DNA replication. 

MACKE CASE Modeling Unusual Nucleic Acid Structures... 

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