DNA solvents

Fig.8. Effect of tilorone and congeners on the thermal transition temperature (Tm) of calf thymus DNA. Solvent is 0.01 M Tris-HCl pH 7.0 and the concentrations of DNA-P and congeners are 5 x 10-6M, respectively. Curve 1 = DNA 2 = DNA + MEAA-fluorene 3 = DNA + DEAA-fluorene 4 = DNA + DMAA-dibenzothiophene 5 = DNA + DMAA-dibenzofuran and 6 = DNA + DEAE-fluorenone...

In summary, the picture emerging from these studies suggests that DNA is an extensively hydrated macromolecule the very stmcture of DNA is dictated by its interactions with water. The aggregate results suggest that 10 to 30 waters per phosphate interact with DNA and that these waters can be distinguished from bulk water by various physical observables. DNA hydration, as characterized by physical methods, has been shown to be sequence-, composition-, and conformation-dependent. However, different physical parameters are sensitive to different subpopulations of waters of hydration. As such, different parameters may be complementary but not directly comparable with each parameter providing its own unique window into a particular aspect of DNA-solvent interactions. 

Fig. 19. Effect of tilorone on the thermal transition temperature (Tm) of calf thyms DNA. Solvent is 0.01 M Tris. HC1 (pH 7.0), and the DNA concentration is 5xlO "sM in all experiments. Curve 1 represents the melting profile of DNA in the absence of tilorone, and curve 2 is the melting profile of DNA in the presence of lxlO sM tilorone hydrochloride...

Aqueous Solutions. The concentrated solutions of radioactive DNA (solvent = SSC) were diluted, either in water or in an SSC solution having various concentrations (between 1 and 1/300), and in the presence of variable quantities of non-radioactive carrier DNA (calf thymus or salmon sperm - SIGMA). 

Fig. 6. Intrinsic viscosity of dye-DNA complexes relative to the intrinsic viscosity of DNA alone as a function of the molar ratio dye/DNA. - Solvent O.OIM acetate buffer (pH 5.0). A zoanthoxanthin O norzoanthoxanthin. (From Reference 26.)...

The first term represents the forces due to the electrostatic field, the second describes forces that occur at the boundary between solute and solvent regime due to the change of dielectric constant, and the third term describes ionic forces due to the tendency of the ions in solution to move into regions of lower dielectric. Applications of the so-called PBSD method on small model systems and for the interaction of a stretch of DNA with a protein model have been discussed recently ([Elcock et al. 1997]). This simulation technique guarantees equilibrated solvent at each state of the simulation and may therefore avoid some of the problems mentioned in the previous section. Due to the smaller number of particles, the method may also speed up simulations potentially. Still, to be able to simulate long time scale protein motion, the method might ideally be combined with non-equilibrium techniques to enforce conformational transitions. 

G. Ramachandran and T. Schlick. Solvent effects on supercoiled DNA dynamics explored by Langevin dynamics simulations. Phys. Rev. E, 51 6188-6203, 1995. 

The final class of methods that we shall consider for calculating the electrostatic compone of the solvation free energy are based upon the Poisson or the Poisson-Boltzmann equatior Ihese methods have been particularly useful for investigating the electrostatic properties biological macromolecules such as proteins and DNA. The solute is treated as a body of co stant low dielectric (usually between 2 and 4), and the solvent is modelled as a continuum high dielectric. The Poisson equation relates the variation in the potential (f> within a mediu of uniform dielectric constant e to the charge density p ... 

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. 

Over the next decade a number of efforts were made to apply MD simulations using explicit solvent representations to DNA. A number of these calculations were performed... 

Protein-DNA complexes present demanding challenges to computational biophysics The delicate balance of forces within and between the protein, DNA, and solvent has to be faithfully reproduced by the force field, and the systems are generally very large owing to the use of explicit solvation, which so far seems to be necessary for detailed simulations. Simulations of such systems, however, are feasible on a nanosecond time scale and yield structural, dynamic, and thermodynamic results that agree well with available experimen-... 

Molecular dynamics simulations have also been used to interpret phase behavior of DNA as a function of temperature. From a series of simulations on a fully solvated DNA hex-amer duplex at temperatures ranging from 20 to 340 K, a glass transition was observed at 220-230 K in the dynamics of the DNA, as reflected in the RMS positional fluctuations of all the DNA atoms [88]. The effect was correlated with the number of hydrogen bonds between DNA and solvent, which had its maximum at the glass transition. Similar transitions have also been found in proteins. 

Essential for MD simulations of nucleic acids is a proper representation of the solvent environment. This typically requires the use of an explicit solvent representation that includes counterions. Examples exist of DNA simulations performed in the absence of counterions [24], but these are rare. In most cases neutralizing salt concentrations, in which only the number of counterions required to create an electrically neutral system are included, are used. In other cases excess salt is used, and both counterions and co-ions are included [30]. Though this approach should allow for systematic smdies of the influence of salt concentration on the properties of oligonucleotides, calculations have indicated that the time required for ion distributions around DNA to properly converge are on the order of 5 ns or more [31]. This requires that preparation of nucleic acid MD simulation systems include careful consideration of both solvent placement and the addition of ions. 

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