Conformational stability in dinucleoside phosphate crystals. Semiempirical potential energy calculations for uridylyl-3'-5'-adenosine monophosphate (UpA) and guanylyl-3',5'-cytidine monophosphate (GpC)

Classical potential energy calculations were performed for the dinucleoside phosphates UpA and GpC. Two widely accessible low-energy regions of conformation space were found for the w', w pair. That of lowest energy contains conformations similar to helical RNA, with w' and w in the vicinity of 300° and 280°, respectively. All five experimental observations of crystalline GpC, two of ApU, and the helical fragment of ApApA fall in this range. The second lowest region has w' and w at about 20° and 80°, respectively, which is in the general region of one experimentally observed crystalline conformer of UpA, and the nonhelical region of ApApA. It is concluded that GpC and ApU, which were crystallized as either sodium or calcium salts, are shielded from each other in the crystal by the water of hydration and are therefore free to adopt their predicted in vacuo minimum energy helical conformations. By contrast, crystalline UpA had only 1/2 water per molecule, and was forced into higher energy conformations in order to maximize intermolecular hydrogen bonding

Classical potential energy calculations for ApA, CpC, GpG, and UpU. The influence of the bases on RNA subunit conformations

Classical potential energy calculations have been made for the ribodinucleoside monophosphates ApA, CpC, GpG, and UpU. Van der Waal's, electrostatic, and torsional contributions to the energy were calculated, and the energy was minimized with the seven backbone conformational angles as simultaneously variable parameters. At the global minimum, ApA and CpC have conformations like double helical RNA: the angles ω′ and ω are g−g−, the sugar pucker is C3′-endo, and the bases are anti. GpG and UpU, on the other hand, have the ω′,ω angle pair g−t at the global minimum, and for GpG the bases are syn. Energy contour maps for ω′ and ω show two broad, low energy regions for ApA, CpC, and UpU: one is g−g−, and the second encompasses g−t and g+g+ within a single low energy contour. The two regions are connected by a path at 10–13 kcal./mole. For GpG, with bases syn, however, only a small low-energy region at g−t is found. The helical ‘A’ RNA conformation is 8.5 kcal/mole higher for this molecule. Thus, the base composition is shown to influence the conformations adopted by dinucleoside phosphates. Comparison of calculations with experimental data, where available, show good agreement

Structure of guanosine-3′,5′-cytidine monophosphate. I. Semi-empirical potential energy calculations and model-building

The conformation and packing scheme for guanosine-3’,5’-cytidine monophosphate, GpC, were computed by minimizing the classical potential energy. The lowest energy conformation of the isolated molecule had dihedral angles in the range of helical RNA’s, and the sugar pucker was C3‘ endo. This was used as the starting conformation in a packing search over orientation space, the dihedral angles being flexible in this step also. The packing search was restricted by constraints from our x-ray data, namely, (1) the dimensions of the monoclinic unit cell and its pseudo-C2 symmetry (the real space group is P21), (2) t,he location of the phosphorous atom, and (3) the orientation of the bases. In addition, a geometric function was devised to impose Watson-Crick base pairing. Thus, a trial structure could be sought without explicit inclusion of intermolecular potentials. An interactive computer graphics system was used for visualizing the calculated structures. The packing searches yielded two lowest energy schemes in which the molecules had the same conformation (similar to double-helical RNA) but different orientations within the unit cell. One of these was refined by standard x-ray methods to a discrepancy index of 14.4% in the C2 pseudocell. This served as the starting structure for the subsequent refinement in the real P21 cell

The crystal and molecular structure of a calcium salt of guanylyl-3',5'-cytidine (GpC)

The calcium salt, Ca(C_19H_24N_8O_I2P)_2.18H_20, of guanylyl-3',5'-cytidine (GpC) has been refined to an R of 8·2 % for 2918 observed reflections (11% for 4237 reflections, including unobserved). The molecule crystallized in space group P2_1 with a=21·224, b=34·207, c=9·327 Å, β=90·527°, Z=4. The asymmetric unit contains four GpC, 36 waters and two Ca^2+ ions, for a total of 198 non-hydrogen atoms. The four GpC occur as two dimers related by a pseudo C-face-centering. Each dimer consists of two crystallographically independent GpC as Watson-Crick base-pairs, and possesses a pseudo twofold axis broken by a Ca^2+ ion and associated solvent. The structure was solved by an unusual series of steps including semi-empirical potential-energy methods, packing analysis, rigid-body refinement, least-squares and difference Fourier techniques, and direct-methods tangent-formula phase refinement. The four GpC have conformational angles in the range of helical RNA, but are not identical. The different crystallographic environments perturb the GpC from exact symmetry and demonstrate the range of the basic helical conformations. All eight bases are anti, sugars are all C(3’) endo, the C(4')-C(5') bond rotations are gauche-gauche, and the ω', ω angle pair about the O-P bonds is gauche—gauche-

Conformation of Guanosine Cytidine 3',5'-Monophosphate (GpC)

A brief communication of preliminary results of solution of dinucleoside phosphate GpC

Structure of guanylyl-3′,5′-cytidine monophosphate. II. Description of the molecular and crystal structure of the calcium derivative in space group P2₁

The structural features of calcium guanosine-3′,5′-cytidine monophosphate (GpC) have been elucidated by X-ray diffraction analysis. The molecule was crystallized in space group P2₁ with cell constants of a = 21.224 Å, b = 34.207 Å, c = 9.327 Å, and β = 90.527°, Z = 8. The hydration of the crystal is 21% by weight with 72 water molecules in the unit cell. The four GpC molecules in the asymmetric unit occur as two Watson-Crick hydrogen-bonded dimers related by a pseudo-C face centering. Each dimer consists of two independent GpC molecules whose bases are hydrogen bonded to each other in the traditional Watson-Crick fashion. Each dimer possesses a pseudo twofold axis broken by a calcium ion and associated solvent. The four molecules are conformationally similar to helical RNA, but are not identical to it or to each other. Instead, values of conformational angles reflect the intrinsic flexibility of the molecule within the range of basic helical conformations. All eight bases are anti, sugars are all C3′-endo, and the C4′-C5′ bond rotations are gauche-gauche. The R factor is 12.6% for 2918 observed reflections at 1.2-Å resolution

DNA Backbone Conformation in Cis-Syn Pyrimidine[ ]Pyrimidine Cyclobutane Dimers

A theoretical calculation involving minimization of energy functions was made to determine the conformation of a deoxydinucleoside monophosphate pyrimidine[ ]pyrimidine cis-syn cyclobutane dimer. Such single-stranded moieties are useful models for the in uiuo situation because single strands are more easily damaged, and the damage inhibits the normal function of single-stranded replicating DNA. The calculated minimum-energy conformer was incorporated in a mode l of B-DNA to assess the influence of this covalent lesion on the normal form of DNA

Metropolis simulations of Met-Enkephalin with solvent-accessible area parameterizations

We investigate the solvent-accessible area method by means of Metropolis simulations of the brain peptide Met-Enkephalin at 300$K$. For the energy function ECEPP/2 nine atomic solvation parameter (ASP) sets are studied. The simulations are compared with one another, with simulations with a distance dependent electrostatic permittivity $\epsilon (r)$, and with vacuum simulations ($\epsilon =2$). Parallel tempering and the biased Metropolis techniques RM$_1$ are employed and their performance is evaluated. The measured observables include energy and dihedral probability densities (pds), integrated autocorrelation times, and acceptance rates. Two of the ASP sets turn out to be unsuitable for these simulations. For all other systems selected configurations are minimized in search of the global energy minima, which are found for the vacuum and the $\epsilon(r)$ system, but for none of the ASP models. Other observables show a remarkable dependence on the ASPs. In particular, we find three ASP sets for which the autocorrelations at 300$$K are considerably smaller than for vacuum simulations.Comment: 10 pages and 8 figure

Effective interaction between helical bio-molecules

The effective interaction between two parallel strands of helical bio-molecules, such as deoxyribose nucleic acids (DNA), is calculated using computer simulations of the "primitive" model of electrolytes. In particular we study a simple model for B-DNA incorporating explicitly its charge pattern as a double-helix structure. The effective force and the effective torque exerted onto the molecules depend on the central distance and on the relative orientation. The contributions of nonlinear screening by monovalent counterions to these forces and torques are analyzed and calculated for different salt concentrations. As a result, we find that the sign of the force depends sensitively on the relative orientation. For intermolecular distances smaller than $6\AA$ it can be both attractive and repulsive. Furthermore we report a nonmonotonic behaviour of the effective force for increasing salt concentration. Both features cannot be described within linear screening theories. For large distances, on the other hand, the results agree with linear screening theories provided the charge of the bio-molecules is suitably renormalized.Comment: 18 pages, 18 figures included in text, 100 bibliog