Ihosvany Camps holds a Bachelor degree in Physics from the Faculty of Physics, University of Havana (Cuba, 1995), Master degree in Physics from the Faculty of Physics, University of Havana (Cuba, 1996) and a PhD in Physics from the Institute of Physics, Federal Fluminense University (Brazil, 2001). Has experience in Condensed Matter Physics and Computational Modelling. Currently, has as main research lines the study of electronic properties of nanostructures and the molecular modelling of organic and inorganic systems including the modelling of drugs (rational drug design, fragment-based drug design, and de novo design), molecular docking, and studies on polymorphism of pharmaceutical solids.
In this work we made use of the fragment-based drug design (FBDD) and de novo design to obtain more powerful acetylcholinesterase (AChe) inhibitors. The acetylcholinesterase is associated to the Alzheimer’s Disease (AD). It was found that the cholinergic pathways in the cerebral cortex is compromised in AD and the accompanying cholinergic deficiency contributes to the cognitive deterioration of AD patients. In the FBDD approach, fragments are docked into the active site of the protein. As fragments are molecular groups with low number of atoms, it is possible to study they interaction with localized amino acids. Once the interactions are measured, the fragments are organized by affinity and then linked between them to form new molecules with high degree of interaction with the active site. In the other approach, we used the de novo design technique starting from reference drugs used in the AD treatment. These drugs were break into fragments (seeds). In the growing strategy, fragments were add to each seed growing new molecules. In the linking strategy, two or more separated seeds are linked with different fragments. Both strategies produced a library of more than 2M compounds. This library was filtered using ADME properties. The resulting library with around 6k compound was filtered again. In this case, structures with Tanimoto coefficient greater than 0.85 were discarded. The final library with 1.5k compounds was submitted to docking studies. As a result, 10 compounds with better interaction energy than the reference drugs were obtained. We acknowledge financial support of FAPEMIG.
Chan-Shing Lin has completed his PhD at University of California, Irvine, in 1992. He has published more than 65 papers in reputed journals and has been serving as an Editorial Board Member of Archive of Virology and Frontier journals. He has also consulted biotechnology companies in building the cGMP processes for manufacturing vaccines and bio-medicals.
The virus-like particle (VLP) assembled from capsid subunits of the dragon grouper nervous necrosis virus (DGNNV) is very similar to its native T=3 virion, in addition that the VLPs can enter fish cells with macropinocytosis way. Furthermore, the disulfide bounds are not essential for the VLP formation, whereas cations are involved in the VLP stability in vitro. At pH 8.0, the VLPs can be precipitated with EDTA at room temperature. In weak basic condition, cryoEM model of the capsid protein (52-213th amino acids) at 3.56 Å resolution reveals calcium-ion bridges and unique cation-π interactions. Submersion of VLP crystals in cations provide sharper diffraction intensity than control and enhanced the radiation damage. All together supports that cations stabilize the viral particle by holding three subunits in an asymmetric unit of trimer.