Miguel X. Fernandes

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Nonspherical particles or molecules experience an ordering effect in the presence of obstacles due to the restrictions they place on the orientation of those molecules that are in their proximity. Obstacles may be the limits of a membrane in which the molecule is embedded, oriented mesoscopic systems such as bicelles, or membrane fragments used to induce(More)
The potential of antimicrobial peptides (AMPs) as an alternative to conventional therapies is well recognized. Insights into the biological and biophysical properties of AMPs are thus key to understanding their mode of action. In this study, the mechanisms adopted by two AMPs in disrupting the gram-negative Escherichia coli bacterial envelope were explored.(More)
Hydrodynamic properties (translational diffusion, sedimentation coefficients and correlation times) of short B-DNA oligonucleotides are calculated from the atomic-level structure using a bead modeling procedure in which each non-hydrogen atom is represented by a bead. Using available experimental data of hydrodynamic properties for several oligonucleotides,(More)
We have developed a Brownian dynamics simulation algorithm to generate Brownian trajectories of an isolated, rigid particle of arbitrary shape in the presence of electric fields or any other external agents. Starting from the generalized diffusion tensor, which can be calculated with the existing HYDRO software, the new program BROWNRIG (including a(More)
Computer-assisted drug design (CADD) is a valuable approach for the discovery of new chemical entities in the field of cancer therapy. There is a pressing need to design and develop new, selective, and safe drugs for the treatment of multidrug resistance (MDR) cancer forms, specifically active against P-glycoprotein (P-gp). Recently, a crystallographic(More)
P-glycoprotein (P-gp) is one of the best characterized transporters responsible for the multidrug resistance phenotype exhibited by cancer cells. Therefore, there is widespread interest in elucidating whether existing drugs are candidate P-gp substrates or inhibitors. With this aim, a pharmacophore model was created based on known P-gp inhibitors and it was(More)
The virtual screening of a library of xanthone derivatives led us to the identification of potential novel MDM2 ligands. The activity of these compounds as inhibitors of p53-MDM2 interaction was investigated using a yeast phenotypic assay, herein developed for the initial screening. Using this approach, in association with a yeast p53 transactivation assay,(More)
The acquisition of drug-resistant mutations by infectious pathogens remains a pressing health concern, and the development of strategies to combat this threat is a priority. Here we have applied a general strategy, inverse design using the substrate envelope, to develop inhibitors of HIV-1 protease. Structure-based computation was used to design inhibitors(More)
Naturally occurring xanthones have been documented as having antitumor properties, with some of them presently undergoing clinical trials. In an attempt to improve the biological activities of dihydroxyxanthones, prenylation and other molecular modifications were performed. All the compounds reduced viable cell number in a leukemia cell line K-562, with the(More)
Cells in living organisms are regulated by chemical and physical stimuli from their environment. Often, ligands interact with membrane receptors to trigger responses and Sargent and Schwyzer conceived a model to describe this process, “membrane catalysis”. There is a notion that the physical organization of membranes can control the response of cells by(More)