RESUMO
Human immunodeficiency virus type 1 (HIV-1) protease (PR) plays an essential role in the life cycle of the virus. Consequently, its inhibition can control acquired immunodeficiency syndrome (AIDS). Any pharmacological treatment targeting the active site of the protease is known to generate escape mutants. On the other hand, if a drug targets a site crucial for the correct folding of the protease, mutations affecting this region would denaturate the protein and thus will not be expressed. We review the progress in our understanding of the folding of the protease, which has been instrumental in the design of a (non-conventional) folding inhibitor. The transferability of these results to other proteins testify to the universality of the folding-inhibition scenario for the design of leads of drugs which are unlikely to generate resistance.
Assuntos
Inibidores da Protease de HIV/química , Protease de HIV/química , Animais , Desenho de Fármacos , Farmacorresistência Viral , Protease de HIV/metabolismo , Inibidores da Protease de HIV/farmacologia , Humanos , Cinética , Modelos Moleculares , Conformação Proteica , Dobramento de Proteína , Estrutura Terciária de ProteínaRESUMO
We develop a scheme to exactly evaluate the correlation energy in the random-phase approximation, based on linear response theory [Y. R. Shimizu, J. D. Garrett, R. A. Broglia, M. Gallardo, and E. Vigezzi, Rev. Mod. Phys. 61, 131 (1989)]. It is demonstrated that our formula is equivalent to a contour integral representation recently proposed [F. Donau, D. Almehed, and R. G. Nazmitdinov, Phys. Rev. Lett. 83, 280 (1999)] being numerically more efficient for realistic calculations. Examples are presented for pairing correlations in rapidly rotating nuclei.
RESUMO
A systematic microscopic study of the anharmonic properties of the double giant dipole resonance (DGDR) has been carried out, for the first time, for nuclei with mass number A spanning the whole mass table. It is concluded that the corrections of the energy centroid of the Jpi = 0(+) and 2(+) components of the DGDR from its harmonic limit are negative, have a value of the order of a few hundred keV, and follow an A-1 dependence.
RESUMO
The coupling of vibrations to nucleons moving in levels lying close to the Fermi energy of deformed rotating nuclei is found to lead to a number of effects: (i) shifts of the single-particle levels of the order of 0.5 MeV towards the Fermi energy and thus to an increase of the level density, (ii) single-particle state depopulation of the order of 30%, and thus spectroscopic factors approximately 0.7, etc. These effects, which we have calculated for 168Yb, can be expressed in terms of an effective mass, the so-called omega mass ( m(omega)), which is approximately 40% larger than the bare nucleon mass in the ground state. It is found that m(omega) displays a strong dependence with rotational frequency, eventually approaching the bare mass for Planck's over 2piomega(rot) approximately 0.5-0.6 MeV.