RESUMO
It was shown that the kinetics of changes of γH2AX foci number (marker of DNA double-strand breaks) in human skin fibroblasts after exposure to low doses of X-ray radiation (20, 40 and 80 mGy) differs from that observed after exposure to medium-low doses (160 and 240 mGy). After exposure to 160 and 240 mGy the highest number of γH2AX foci was detected at 30 min after exposure (first experimental point) and further their decrease was observed. At the same time we observed a fast phase of repair (upto 4 h), in which there was a decrease of the foci amount to ~50-60% and a slow phase of repair (from 4 h to 24 h). After 24 h only ~3-5% of the foci amount observed at 30 min after irradiation was left. After exposure to low doses, the foci number did not decrease during 2 h and even 24 h after exposure their amount was ~25% from that observed at maximum points (1 h after irradiation at 40 and 80 mGy and 2 h after irradiation at 20 mGy).
Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA , Fibroblastos/efeitos da radiação , Histonas/genética , Pele/efeitos da radiação , Raios X/efeitos adversos , Células Cultivadas , Relação Dose-Resposta à Radiação , Fibroblastos/patologia , Voluntários Saudáveis , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Pele/patologia , Fatores de TempoRESUMO
Knowledge of 3D-structure of protein-ligand complex is a major prerequisite for understanding the functioning mechanism of cellular proteins and membrane receptors. This is also of a great help in rational drug design projects. In the present paper we briefly review the molecular docking approaches used to predict possible orientation of a ligand in the protein binding site. The recent trends to improve the accuracy and efficiency of docking algorithms are demonstrated with the results obtained in Laboratory of Biomolecular Modeling. Particular attention is paid to protein-ligand hydrophobic and stacking interactions responsible for molecular recognition of ligand fragments. Such type of interactions are not always adequately represented in scoring criteria of docking applications that leads to mismatch in 3D-structure complexes predictions. That is why further inquiry of methods to account for these interactions is now the area of active research.