A study of the hydration of deoxydinucleoside monophosphates containing thymine, uracil and its 5-halogen derivatives: Monte Carlo simulation.

An extensive Monte Carlo simulation of hydration of various conformations of the dinucleoside monophosphates (DNP), containing thymine, uracil and its 5-halogen derivatives has been performed. An anti-anti conformation is the most energetically stable one for each of the DNPs. In the majority of cases the energy preference is determined by water-water interaction. For other dimers conformational energy is the most important factor, or both the factors are of nearly equal importance. The introduction of the methyl group into the 5-position of uracil ring most noticeably influences the conformational energy and leads to the decrease of its stabilizing contribution to the total interaction energy. The introduction of halogen atoms increases the relative content of anti-syn and syn-anti conformations of DNPs as compared to the parent ones due to the formation of an energetically more favorable water structure around these conformations. A correlation is observed between the Monte Carlo results for the halogenated DNPs and their experimental photoproduct distribution. The data obtained demonstrates a sequence dependence in the photochemistry of the halogenated dinucleoside monophosphates.

Protein-nucleic acid recognition: simulation of base and "model" amino acids complexes in DMSO by the Monte Carlo method.

A computer simulation of guanine (G), cytosine (C), the G-C base pair, protonated C (CH+), acetic acid in neutral (AcOH) and deprotonated (AcO-) forms, G-AcO-, C-AcOH, and CH(+)-AcO- complexes, solvated in DMSO was carried out by the Monte Carlo method. It is shown that the G-C base pair formation in DMSO is energetically favorable. The G-AcO- complex formation is comparable with the formation of G-C base pair in energetically favorability. In this case the acetate anion can replace C in the G-C base pair. The formation of the C-AcOH complex is much less favorable than the formation of the G-C pair. However proton transfer from AcOH to C leads to the formation of the CH(+)-AcO- complex, which is the most favorable of all complexes studied. Here the acetic acid can replace G in a G-C base pair. The formation of G-AcO- and CH(+)-AcO- specific complexes detected in DMSO with the help of experiment and theory is a competitive process with respect to the formation of G-C base pairs, and can be considered the primary step in the real mechanism of protein-nucleic acid recognition.

The study of the stability of Watson-Crick nucleic acid base pairs in water and dimethyl sulfoxide: computer simulation by the Monte Carlo method.

An extensive computer simulation of nucleic acid bases and Watson-Crick base pairs in a water cluster and DMSO cluster is performed by the Monte Carlo method. It is demonstrated that the unfavorable energetics of pair formation in a water cluster is determined by the significant destabilizing contribution of solvent to the energy of complex formation. It is shown that the formation of coplanar base pairs in a DMSO cluster is favorable. The DMSO cluster stabilizes A-U and A-T base pairs and the insignificant destabilization of the G-C base pair by a DMSO cluster is much less than the stabilization which occurs due to the attraction between bases.

Theoretical investigation of excimer and exciplex states of uracil and halogen derivatives: effect of nonparallelism of bases.

Theoretical modeling of initial steps of the photodimerization mechanism of uracil, 5-methyl-and 5-halogen derivatives was performed. The interaction energy of bases in stacked dimers in the ground and lowest excited states was calculated as a function of the distance between the base planes and of the rotation angles within the perturbation theory for the extended Hückel treatment. The existence of excimer and exciplex region on the potential surface of the excited state was revealed. The excimer (exciplex) geometry has the planes nonparallel with more close contact of the C5-C6 bonds as compared to the ground state of dimers. The results provide new information useful for understanding the photodimerization mechanism of bases and testifies that the singlet excimer state can be a precursor of the photodimerization reaction.

A Monte Carlo simulation of hydration of xanthine-derivatives and their stacked forms.

Results on a Monte Carlo simulation of the hydration of monomer and possible stacked dimer forms of a purine alkaloid series in 200- and 400-water molecule clusters are presented. Investigation of different purine stacked dimers in a 200-water molecule cluster reveals that for caffeine there exists one, for theophylline two and for theobromine four dimers are energetically favorable. For caffeine, the same energetically favored stacked dimer form is observed in both the 200- and 400-water molecule cluster. The main factor stabilizing the preferred dimer stacks is the change in the interaction between water molecules of the monomer cluster and those water molecules in the dimer cluster.