Z1-2000 — Final report
1.
Inherent stereospecificity in the reaction of aflatoxin B1 8,9-epoxide with deoxyguanosine and efficiency of DNA catalysis

Kinetic analysis of guanine alkylation by aflatoxin B1 exo-8,9-epoxide, the reactive form of the hepatocarcinogen AFB1, shows the reaction to be ) 2000 times more efficient in DNA than in aqueous solution, that is, with free 2′-deoxyguanosine. Thermodynamic analysis reveals AFB1 intercalation as the predominant source of the observed DNA catalytic effect. However, the known exo ) endo epoxide stereospecificity of the DNA alkylation is observed even with free deoxyguanosine (ratio ) 20:1 determined by LC-MS and NMR measurements), as beforehand predicted by our theoretical calculations.

COBISS.SI-ID: 4132890
2.
Steric and electrostatic effects at the C2 atom substituent influence replication and miscoding of the DNA deamination product deoxyxanthosine and analogs by DNA polymerases

Deoxyinosine and deoxyxanthosine (dX) are both formed in DNA at appreciable levels in vivo by deamination of deoxyadenosine and deoxyguanosine and can miscode. The replicative bacteriophage T7 DNA polymerase/exonuclease and the translesion DNA polymerase Sulfolobus solfataricus pol IV were used as models to discern the mechanisms of miscoding by DNA polymerases. Linear activity models show the effects of oxygen (dX) and the halogens at C2 on both DNA polymerases as mainly due to a combination of both steric and electrostatic factors, producing a clash with the paired cytosine O2 atom.

COBISS.SI-ID: 4199450
3.
Dynamic behavior of avian influenza A virus neuraminidase subtype H5N1 in complex with oseltamivir, zanamivir, peramivir, and their phosphonate analogues

Molecular dynamics simulations of the neuraminidase N1 in complex with six inhibitors – oseltamivir, zanamivir, peramivir, and their phosphonate analogues – were carried out, the resultant trajectories were analyzed in terms of important interactions, and the corresponding free energies of the flexible 150-loop closing were calculated.

COBISS.SI-ID: 4257306
4.
Microwave Catalysis Revisited: An Analytical Solution

This article represents a continuation of our ongoing effort toward quantitative understanding of the microwave catalytic effect. It provides a derivation of an analytical solution for the microwave catalysis. The obtained expression is compared with the results of the Monte Carlo simulation and is applied to reproduce the microwave catalytic effect experimentally observed in the polyethylene terephthalate solvolysis. Implications for the interactions of microwaves with living organisms in the context of widespread mobile telephony are also discussed.

COBISS.SI-ID: 1851882
5.
DNA Duplex Stability: The Role of Preorganized Electrostatics

The insertion of a DNA base moiety at the end of a DNA duplex to form a Watson-Crick or wobble pair during DNA annealing or replication is a step of fundamental biological importance. Thus we investigated the energetics of a formation of the terminal G·C, G· T, and G·A base pairs using calorimetry and computer simulations. The energies calculated along classical MD trajectories in aqueous solution were analyzed in the framework of Linear Response Approximation to obtain relative free energies for the base insertion and their electrostatic, dispersion, and preorganization components.

COBISS.SI-ID: 33744645