Chapter 6 Molecular Modeling and Atomistic Simulation of Nucleic Acids

Publisher Summary This chapter discusses the molecular modeling and atomistic simulation of nucleic acids. Molecular modeling and biomolecular simulation methods have been increasingly applied to give insight into nucleic acid structure, dynamics, and interaction. This includes the simulation of RNA and DNA alone, bound to proteins and interacting with drugs, in various damaged and modified forms and in different environments ranging from the gas phase to varied solvent and ionic environments. Several methods have also been shown to give detailed insight into nucleic acid dynamics, including the coupled motions in the DNA backbones. Base pair opening has also received considerable attention through the application of umbrella sampling methods that allow the estimations of the potential of mean force for opening the pair. A clear success of the methods has been demonstrated by the Beveridge and Bolton groups, who provided detailed comparison between MD-calculated and NMR-observed properties of the duplex d(CGCGAATTCGCG) 2 in solution. Their results show that the 2D NOESY volumes and scalar coupling constants back calculated from a 14-ns MD simulation are in better agreement with the nuclear magnetic resonance data than back calculations based on canonical A-DNA, B-DNA, or crystal geometries of the same duplex.

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