Nucleic acids, forces

To date, a number of simulation studies have been performed on nucleic acids and proteins using both AMBER and CHARMM. A direct comparison of crystal simulations of bovine pancreatic trypsin inliibitor show that the two force fields behave similarly, although differences in solvent-protein interactions are evident [24]. Side-by-side tests have also been performed on a DNA duplex, showing both force fields to be in reasonable agreement with experiment although significant, and different, problems were evident in both cases [25]. It should be noted that as of the writing of this chapter revised versions of both the AMBER and CHARMM nucleic acid force fields had become available. Several simulations of membranes have been performed with the CHARMM force field for both saturated [26] and unsaturated [27] lipids. The availability of both protein and nucleic acid parameters in AMBER and CHARMM allows for protein-nucleic acid complexes to be studied with both force fields (see Chapter 20), whereas protein-lipid (see Chapter 21) and DNA-lipid simulations can also be performed with CHARMM. 

The methodological advances just presented have brought the field of nucleic acid force field calculations to a point where results from the calculations can be used with reasonable confidence to aid in the interpretation of experimental data as well as to be used for scientific investigations that are not accessible to experiment. Accordingly, a number of studies based on MD simulations, as well as other methods, have been undertaken to study a wide array of biologically relevant events associated with DNA. A brief overview of some of these efforts follows. 

Langley DR (1998) Molecular dynamic simulations of environment and sequence dependent DNA conformations the development of the BMS nucleic acid force field and comparison with experimental results, J Biomol Struct, 16 487—509... 

Molecular mechanics is broken down into several parts in this Encyclopedia. The qualitative aspects of the subject predate computational chemistry, and are to be found in Conformational Analysis 1 Conformational Analysis 2 and Conformational Analysis 3. A brief introduction to molecular mechanics itself is given in Force Fields A Brief Introduction. Molecular dynamics is discussed in many articles, including Molecular Dynamics Techniques and Applications to Proteins. Much of the remainder of molecular mechanics is concerned with, force fields and is summarized in Force Fields A General Discussion, or under the specific type of compound involved, e.g., carbohydrates (see Carbohydrate Force Fields) or nucleic acids (see Nucleic Acid Force Fields). 

The main features of the nucleic acid force fields presently used will be given below. Since the field is relatively large and still under development only the very recent achievements will be covered here. Firstly, the most widely used force fields, AMBER, CHARMM, GROMOS, FLEX, OPLS, will be described. Secondly, the other force fields, used mainly by their authors, will be characterized briefly. A review of the force fields for nucleic acids used before 1987 can be found in the monograph of McCammon and Harvey. ... 

The CHARMM (Chemistry at Harvard macromolecular mechanics) force field has been developed in the laboratory of Karplus (see CHARMM The Energy Function and Its Parameterization). The first, 1983, version was designed as a united type force field for protein and nucleic acids, where hydrogens of the CH3, CH2, and CH groups were treated implicitly. This approximation was important in protein modeling, but is inessential in the case of nucleic acid calculations. An improved all-atom model, specifically designed for the nucleic acids has been presented in 1986. Recently, in 1995, another reparametrized version of the CHARMM nucleic acid force field has been published. ... 

There are many applications for the nucleic acid force fields. They have been applied to study structures and dynamics of the normal, modified, and mismatched oligonucleotide duplexes and triplexes they have also been used in the structure refinement by molecular dynamics method with NMR distance restraints. The force fields have also been widely used in modeling the drug-DNA and the protein-DNA and RNA interactions, as well as in many other problems of pharmacological interest. 

Nevertheless, the current nucleic acid force fields allow molecular simulations to approach the accuracy obtainable from experimental crystallography and NMR techniques. Predictions of a variety of properties for the oligonucleotides in such calculations seem to become respectable. 

Mechanics Nucleic Acid Force Fields Structure-Activity... 

Data Correlation with Chemical Structure NMR Refinement Nucleic Acid Conformation and Flexibility Modeling Using Molecular Mechanics Nucleic Acid Force Fields Nucleic Acids Qualitative Modeling Object-oriented Programming. 

Free Energy Calculations Methods and Applications Free Energy Perturbation Calculations Free Energy Simulations Hydrogen Bonding 1 Hydrogen Bonding 2 Molecular Dynamics DNA Molecular Dynamics Simulations of Nucleic Acids Molecular Dynamics Techniques and Applications to Proteins Nucleic Acid Force Fields Poisson-Boltzmann Type Equations Numerical Methods Protein Force Fields. 

Because the accuracy of molecular mechanics is critically dependent on the parameters used for such studies, a careful choice of parameters must be made. Thus, the first group of articles covers force fields for molecular mechanics and dynamics and contains articles by Cieplak Nucleic Acid Force Fields), MacKerell Protein Force Fields), and Woods Carbohydrate Force Fields),... 

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