Evidences for reaction mechanism of 9DB1 DNA catalyst.

The first reported reaction mechanism of a DNAzyme, i.e. 9DB1, by using molecular dynamics (MD) simulations includes some ambiguities. We try to overcome some of these ambiguous aspects such as the role of mono and divalent metal ions and observed metal rescue effects by surveying the role of functional groups of original 9DB1 and a variety of its rate conserving and rate decreasing mutations via MD simulations. Conformational differences of these two distinct groups are responsible for their opposite rate trends. Blocking of the OH3' of acceptor nucleotide from effective attack by its hydrogen bond to O4' of donor nucleotide is observed in rate decreasing mutations. Our simulations manifest the role of Na+ and Mg2+ ions in bringing close to each other the ligated atoms. These findings along with observed conformational changes explain carefully the reported metal rescue effects for some phosphate groups.

Potential effective inhibitory compounds against Prostate Specific Membrane Antigen (PSMA): A molecular docking and molecular dynamics study.

One of the most prevalent cancers in men is prostate cancer and could be managed with immunotoxins or antibody treatment. Because of the substantial rise of the Prostate-Specific Antigen and the Prostate-Specific Membrane Antigen (PSMA), cancer vaccination should be rendered with these antigens. Through pharmacodynamic experiments in a library of natural compounds from ZINC database, the current research sought to identify compounds that could suppress PSMA protein. To test the most productive compounds for further research, the Library has been scanned with Pharmacophore and ADMET analysis followed by molecular docking methods in the first phase. After selecting 15 ligands with the best pose related to docking results, to evaluate the stability of the ligand-protein bounds of the compounds, a molecular dynamics simulation considering the effect of the presence of zinc ions on the protein structure was performed. The measurement of ligand binding modes and free energy has shown that four compounds, including Z10, Z06, Z01, and Z03, have formed critical interactions with the active site's residues. Besides, multiple approaches were employed to determine their inhibition rating and describe the variables that facilitate the attachment of ligands to the protein active site. The results are obtained from the MMPBSA/GBSA analysis of four selected small molecules (Z10, Z06, Z01, and Z03), which are very close to the IC50 value of reference ligand (DCIBzl); they are -13.85 kcal/mol, -12.58 kcal/mol, -10.71 kcal/mol and -9.39 kcal/mol respectively. Finally, we evaluate the results obtained from selected ligands using hydrogen bond and decomposition analyzes. We have examined the effective interactions between ligands and S1/S1'pockets in protein. Our computational results illustrate the design of more efficient inhibitors of PSMA.

Relative Populations of Some Tautomeric Forms of 2'-Deoxyguanosine-5-Fluorouridine Mismatch.

The importance of the 2'-deoxyguanosine-uridine mispair as the most occurring mismatch in transcriptional studies of RNAs from DNAs is multiplied when 5-halo-substituted uridine species cause a serious increase in the probability of its occurrence. Many studies relate this higher probability to the existence of possible tautomeric and ionic forms of its constituent bases. According to these statements, relative populations of mismatches between 5-fluorouridine and both keto and enol forms of 2'-deoxyguanosine are computed by using a conformational search. In order to have a complete scan of all of the highly probable conformers in a moderate computational time, an extensive conformational search methodology is employed here, which benefits from the advantages of both the molecular dynamics simulations and quantum mechanics calculations. The population of an enolic tautomer of normal wobble orientation is about 0.057% of that of its keto tautomer, whereas the population of an enolic tautomer of reverse wobble orientation is about 0.0054% of that of its keto tautomer. Totally, the reverse wobble orientation is about six times more populated than the normal wobble orientation. Calculated populations are in good agreement with experimental populations of closely related compounds. The reliability of the applied methodology is certified, in part, by a good agreement obtained between some experimental data and corresponding Boltzmann-weighted average data of most probable conformers such as NMR parameters. The validation of this methodology is certified with high accuracy by applying it on the substituted diuridine pairs, where experimental populations are available. Not only are the calculated populations and NMR parameters of this test in very good agreement with the experimental data, but also they are free of the ambiguities mentioned by experimentalists.

Assignment of absolute configuration of 8α-hydroxy-13-hydroperoxylabd-14,17-dien-19,16;23,6α-diolide by computed NMR chemical shifts.

Unassigned configurations of 8α-hydroxy-13-hydroperoxylabd-14,17-dien-19,16;23,6α-diolide, extracted from Iranian salvia, in the C13 and C16 were assigned as S and R, respectively. Extensive ab initio calculations followed by chemical shift predictions were employed in this assignment. Predicted chemical shifts were correlated to experimental ones in order to find the correct configuration, shown here.

Magnetic resonance tensors in uracil: calculation of 13C, 15N, 17O NMR chemical shifts, 17O and 14N electric field gradients and measurement of 13C and 15N chemical shifts.

The experimental (13)C NMR chemical shift components of uracil in the solid state are reported for the first time (to our knowledge), as well as newer data for the (15)N nuclei. These experimental values are supported by extensive calculated data of the (13)C, (15)N and (17)O chemical shielding and (17)O and (14)N electric field gradient (EFG) tensors. In the crystal, uracil forms a number of strong and weak hydrogen bonds, and the effect of these on the (13)C and (15)N chemical shift tensors is studied. This powerful combination of the structural methods and theoretical calculations gives a very detailed view of the strong and weak hydrogen bond formation by this molecule. Good calculated results for the optimized cluster in most cases (except for the EFG values of the (14)N3 and (17)O4 nuclei) certify the accuracy of our optimized coordinates for the hydrogen nuclei. Our reported RMSD values for the calculated chemical shielding and EFG tensors are smaller than those reported previously. In the optimized cluster the 6-311+G** basis set is the optimal one in the chemical shielding and EFG calculations, except for the EFG calculations of the oxygen nuclei, in which the 6-31+G** basis set is the optimal one. The optimal method for the chemical shielding and EFG calculations of the oxygen and nitrogen nuclei is the PW91PW91 method, while for the chemical shielding calculations of the (13)C nuclei the B3LYP method gives the best results.