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D A Pearlman

Publications and source records attributed to D A Pearlman.

23 records · Page 2Linked to original sources
PubMed1985

Conformational studies of nucleic acids. I. A rapid and direct method for generating furanose coordinates from the pseudorotation angle.

The greatest difficulty in modeling a nucleic acid is generating the coordinates of its furanoses. This difficulty arises from constraints imposed by the closed ring geometries of these sugars. We have developed a new method for modeling these furanose rings. Using this method, the coordinates of a sugar can be obtained quickly and unambiguously for any point on the pseudorotational pathway from one parameter: the phase angle of pseudorotation P. The significant difference between this and previous sugar modeling schemes is that here the endocyclic bond lengths of the five-membered sugar ring are allowed to vary a small amount according to simple, explicit, and experimentally reasonable analytic functions of P. The coefficients of these functions follow from the empirical behavior of the endocyclic bond angles and from geometrical constraints due to ring closure. The ability to model the sugars directly from one parameter greatly facilitates carrying out the global conformational studies on nucleic acid constituents which will be attempted in subsequent papers of this series.

Furans↗
PubMed1985

Conformational studies of nucleic acids. II. The conformational energetics of commonly occurring nucleosides.

We have examined the conformational energetics of the eight most commonly occurring nucleosides--A, U, G, C, dA, dT, dG, dC--as monitored by a semi-empirical energy force field. These are the first reported calculations to completely explore the entire conformational spaces available to all eight major nucleosides using experimentally consistent furanose geometries and an appropriate force field. Central to our approach is the ability to model an experimentally reasonable furanose for each nucleoside directly from only one parameter, the phase angle of pseudorotation P, as described in the previous paper (D.A. Pearlman, and S.-H. Kim, preceeding paper in this issue). This allows us to specify the conformation of a nucleoside by three variables: torsion angle gamma (O5'-C5'-C4'-C3'); torsion angle chi (O4'-C1'-N9/N1-C4/C2); and P. In our study each of these parameters was allowed to vary independently and in small increments over the range 0-360 degrees. The empirically observed preferences for C3'-endo and C2'-endo sugar conformations, for anti and syn values of chi and for staggered (g+, t, g-) values of gamma can be explained on the basis of the energy maps so obtained. Finer details, such as the different conformational preferences of ribonucleosides and deoxyribonucleosides and of purines and pyrimidines, can also be extracted from these maps and are consistent with experiment. The calculations support previous descriptions of pseudorotation as hindered. Statistical Boltzmann population factors for different conformational ranges in gamma, chi, and P, as predicted by the calculations, are consistent with factors obtained from crystallographic data. The excellent results here provide additional support for the suitability of the new sugar modeling technique used.

Carbohydrates↗
PubMedDate not supplied

The calculated free energy effects of 5-methyl cytosine on the B to Z transition in DNA.

We have examined the free energy effects of 5-methylation of cytosine on the B in equilibrium Z conformational equilibrium in DNA. Free energy differences were calculated using the free energy perturbation approach, which uses an easily derived equation from classical statistical mechanics to relate the free energy difference between two states to the ensemble average of the potential energy difference between the states. Calculations were carried both in explicit solvent and (for comparison) in vacuo. The free energy values obtained for the explicit solvent systems are total free energies, with contributions from all parts of the system (solvent + solute), and so are relevant to the B in equilibrium Z transitions observed under real (physiological) conditions. We calculate that in solution, methylation makes the B in equilibrium Z transition more favorable by about -0.4 kcal/mole base pair (bp) in free energy. This value compares well with approximate experimentally derived values of about -0.3 kcal/mole-bp. We also discuss a method for determining the free energy difference between conformational states poorly maintained by a potential energy model. Finally, the effects of methylation on the melting temperature of DNA are examined.

5-Methylcytosine↗