Estudo da estrutura e da solvatação do HNP-3, um antibiótico natural, por dinâmica molecular

The structure and hydration of the HNP-3 have been derived from molecular dynamics data using root mean square deviation, radial and energy distributions. Three antiparallel beta sheets were found to be preserved. 15 intramolecular hydrogen bonds were identified together with 36 hydrogen bonds on the backbone and 35 on the side chain atoms. From the point of view of the hydration dynamics, the analysis shows a high solvent accessibility of the monomer and attractive interactions with water molecules.

Dependência das vias de dissociação unimolecular com a energia interna da molécula de éter dimetílico

Internal energy dependence of the competitive unimolecular dissociation channels of dimethyl ether were studied with the statistical RRKM formalism. The C-O and C-H fission reactions and the 1,2-H and 1,3-H shifts, and 1,1-H2 and 1,3-H2 molecular eliminations are discussed as a function of energy dependence of k a(E*), the microcanonical rate constant for production of transition states. C-O fission is the dominant process while reaction channels involving C-H fission, 1,1-H2 and 1,3-H2 elimination and production of MeOH should be competitive at energies around 400 kJ mol-1. The less favorable process is the channel of CH4 formation.

Análise estrutural de ciclodextrinas: um estudo comparativo entre métodos teóricos clássicos e quânticos

In the present work, we analyzed the accuracy of distinct theoretical methods to reproduce the solid state structures of cyclodextrins. The a, b and g-cyclodextrins (CD) were considered and also their hydrates with included water molecules: a-CD.2H2O, b-CD.10H2O and g-CD.12H2O. The geometries were fully optimized using Molecular Mechanics (MM2), semiempirical (AM1 and PM3) and ab initio (HF/3-21G) methods and quantitatively compared with experimental data from X ray diffraction. The results obtained from the classical MM2 method were in best agreement with the experiment. The semiempirical and ab initio structures were also in satisfactory accordance with the experimental data. In general, the PM3 method was found to be more suitable than the AM1 to describe the CD geometries, mainly when the intramolecular hydrogen bonds are considered.

Estrutura e propriedades de elipticinas

The ellipticines constitute a broad class of molecules with antitumor activity. In the present work we analyzed the structure and properties of a series of ellipticine derivatives in the gas phase and in solution using quantum mechanical and Monte Carlo methods. The results showed a good correlation between the solvation energies in water obtained with the continuum model and the Monte Carlo simulation. Molecular descriptors were considered in the development of QSAR models using the DNA association constant (log Kapp) as biological data. The results showed that the DNA binding is dominated by electronic parameters, with small contributions from the molecular volume and area.

Implementação computacional do modelo carga-fluxo de carga-fluxo de dipolo para cálculo e interpretação das intensidades do espectro infravermelho

The first computational implementation that automates the procedures involved in the calculation of infrared intensities using the charge-charge flux-dipole flux model is presented. The atomic charges and dipoles from the Quantum Theory of Atoms in Molecules (QTAIM) model was programmed for Morphy98, Gaussian98 and Gaussian03 programs outputs, but for the ChelpG parameters only the Gaussian programs are supported. Results of illustrative but new calculations for the water, ammonia and methane molecules at the MP2/6-311++G(3d,3p) theoretical level, using the ChelpG and QTAIM/Morphy charges and dipoles are presented. These results showed excellent agreement with analytical results obtained directly at the MP2/6-311++G(3d,3p) level of theory.

Polarizabilidades e primeira hiperpolarizabilidades elétricas dipolares de ésteres E-4-amino-trans-1,3-butadienil-(1',2'-di-hidroxibenzeno) de boro, alumínio e gálio

Static electric dipole polarizabilities and first hyperpolarizabilites have been calculated for the title molecules and their 3' and 4'-nitro derivatives at ab-initio Hartree- Fock/6-31G(d, p) level. The influence of the pivotal p vacant 3A elements (B, Al or Ga) substitution on the electrical properties of these molecules is detailed. The axial vector components of the first hyperpolarizabilities β(0) of the push-pull 4'-nitro derivatives, -18.2×10-32 esu (B), -21.1×10-32 esu (Al) and -20.8×10-32 esu (Ga) are calculated to be as much as fourfold larger then that calculated for the p-nitroaniline, a reference organic molecule for comparison for this type of molecular property.

Bases moleculares da ação anti-inflamatória dos ácidos oleanólico e ursólico sobre as isoformas da ciclo-oxigenase por docking e dinâmica molecular

The triterpenoids oleanolic (OA) and ursolic (UA) acids show non-selective antiinflamatory activity in vitro for cyclooxygenase (COX) isoforms. 3D conformations of OA and UA, with three possible orientations (1, 1' and 2) in the active site of isoforms COX, obtained by docking, were submitted to molecular dynamics. The results show that orientation 2 of the OA in COX-2 is more favorable because orientation 1 moved away from the active site. The carboxylate group of OA interact by hydrogen bonds with Ser353 and with Phe357 and Leu359, mediated by water, while hydroxyl in C-3 interact by hydrogen bond, mediated by water, with Tyr385.

Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.