Nucleic acids simulations

Darden T A, L Perera, L Li and L Pedersen 1999. New Tricks for Modelers from the Crystallography Toolkit The Particle Mesh Ewald Algorithm and Its Use in Nucleic Acid Simulations. Structure with Folding and Design 7 R55-R60. 

In Section II we provide an overview of the current status of nucleic acid simulations, including studies on small oligonucleotides, DNA, RNA, and their complexes with proteins. This is followed a presentation of computational methods that are currently being applied for the study of nucleic acids. The final section of the chapter includes a number of practical considerations that may be useful in preparing, performing, and analyzing MD simulation based studies of nucleic acids. 

Darden T, Perera L, Li LP, Pedersen L (1999) New tricks for modelers from the crystallography toolkit the particle mesh Ewald algorithm and its use in nucleic acid simulations. Struct Fold Des 7(3) R55-R60... 

In the last example, we move to the general problem of nucleic acid simulations. It is abundantly clear that simulations on DNA double helix... 

The quality of a force field can be established only through extensive test simulations. A large number of force fields that are widely used for biomolecu-lar simulations are available in the literature. These have been used to simulate a variety of systems. For example, the OPLS parameter set developed by Jorgensen et al. ° has been shown to be satisfactory for the simulation of a large number of neat liquid hydrocarbons and polar molecules. Similarly, the AMBER force field nd the CHARMM force field have been used for a variety of protein and nucleic acid simulations. 

In this chapter, we will focus on the development and application of the combined quantum/classical methods. To accomplish this we first provide background on the classical methods used in protein and nucleic acid simulations. In Sect. 2 we review the form and origin of empirical potentials used in biopolymer dynamics, the classical simulation methods, and techniques for evaluating thermodynamic averages as might be important in computing barrier heights for chemical rate processes. Next we describe the basic formalism for mixed quantum/classical simulation methods as well as some of the practical considerations in their development and implementation. This is done in Sect. 3. We conclude in Sect. 4 with an overview of these methods and their potential for chemical studies. 

In slightly more than 10 years since the original protein MD simulation, a number of detailed MD simulations of globular proteins in vacuo, in solution, and in hydrated crystals have been performed. More recently, MD simulations for nucleic acids (DNA and tRNA) have appeared in the literature. °" Nucleic acid simulations can be particularly diallenging due to the complex hydration and polyelectrolyte properties of these molecules, as well as the limited experimental structural data available for these systems. MD simulations of model lipid bilayers and micelles are even less common, " due mainly to the size and complex behavior of these systems. As resources and the sophistication of simulation methods and models continue to improve, MD simulations of larger and more complex biomolecular systems will become commonplace. 

The AMBER software and AMBER force fields are widely used for the simulation of various systems of biological and material science importance. Some researchers develop proper additions and corrections to standard parameters for better description of specific systems. We refer to only two of many such examples. Perez et al. (2007) reparameterized the parm99 force field for nucleic acid simulations, improving the representation of the a/y conformational space, which seems to be poorly represented in very long DNA MD simulations with available AMBER force fields. Song et al. (2008) adjusted the AMBER force field to reproduce conformational properties of an oxidative DNA lesion, 2,6-diamino-4-hydroxy-5-formamidopyrimidine. 

The ENCAD force field has been mainly used for protein simulations but some limited applications to nucleic acids have also been reported DNA dodecamer. Tip rep-DNA, and Homeo rep-DNA complexes. The quality of this force field and its performance in the nucleic acid simulations are yet to be confirmed. One of the problems with this force field, which could be noticed here, is for example the irreversible base pair opening in DNA observed during molecular dynamics simulations. ... 

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