Atomic-level models, nucleic acid

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. 

Of course, the simplicity of the QM/MM operator does not imply diat it has only a small effect. Large atomic partial charges placed near the QM fragment would be expected to polarize the system strongly. Table 13.2 compares the dipole moments of the standard nucleic acid bases at the AMI level evaluated in the gas phase and in a QM/MM calculation carried out modeling aqueous solvation with a periodic box of TIP31 water molecules. Eor comparison, results from the AM1-SM2 aqueous continuum solvation model are also provided. 

Of the three major components of biological structure, the proteins, nucleic acids, and polysaccharides, least is known about the polysaccharides at the secondary and tertiary level of molecular structure. This is because the polysaccharides cannot be obtained in crystals which are large enough for single crystal X-ray or neutron structure analysis. What structural information there is comes from fiber X-ray diffraction patterns. However good these diffraction patterns are, the structures derived from them will always be model-dependent. This is because the number of variable atomic parameters which determine the diffraction intensities exceeds the number of observed intensities. 

Figure 2 Schematic of three levels, including atomistic (a), base-pair level (b), and coarse-grained level (c), for modeling of dsDNA as a representative nucleic acid. Atomic positions used to construct the image in part (a) were found by using the 3DNA software package (found at http //rutchem.rutgers.ed u/xiangjun/3DNA/faq. html). ...

The most fundamental level of modeling of any chemical system employs quantum mechanics. Quantum mechanical (QM) treatments are required to understand many important chemical and biological properties of nucleic acids. Moreover, empirical force-field methods, employed to study the conformations of polynucleotides, rely on quantum calculations to obtain crucial parameters that are difficult to measure experimentally, such as atom-centered charges for calculating electrostatic interactions. The obtain a description of a chemical system using QM one solves the time-independent Schrodinger equation with or without the use of empirical parameters. 

Macromolecular models should have a level of resolution commensurate with the quality and quantity of available data. We have developed a package of programs for building and refining models of nucleic acids and protein-nucleic acid complexes, with different levels of detail in different parts of the molecule. The method incorporates data from a variety of experiments. Our RNA models have atomic detail in some regions and lower resolution (typically one pseudoatom per nucleotide) in others. We are using this approach to refine models for the 308 subunit of the E. coli ribosome, with emphasis on the decoding site, where the 168 rRNA holds the mRNA and two tRNAs. 

The simulation methodologies applied to proteins and nucleic acids are applicable to the biomembrane modeling at the atomic level. The jvidely distributed programs, CHARMM, AMBER, and GROMOS, have been applied for biomembrane studies. The common energy parameters of proteins, nucleic acids, and water are used with minor modifications for lipids. For instance, the AMBER energy function is written as follows ... 

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