Abstract: Bacterial molecular chaperone DnaK plays an essential role in protein folding, stress response and transmembrane targeting of proteins. DnaKs from many bacterial species, including Escherichia coli, Salmonella typhimurium and Haemophilus infleunzae are the molecular targets for the insect-derived antimicrobial peptide pyrrhocoricin. Pyrrhocoricin-like peptides bind in the substrate recognition tunnel. Despite the high degree of crossspecies sequence conservation in the substrate-binding tunnel, some bacteria are not sensitive to pyrrhocoricin. This work addresses the molecular mechanism of resistance of Helicobacter pylori DnaK to pyrrhocoricin. Homology modelling, structural and sequence analysis identify a single aminoacid substitution at the interface between the lid and the β-sandwich subdomains of the DnaK substrate-binding domain as the major determinant for its resistance.
Abstract: A computational platform is presented in this
contribution. It has been designed as a virtual laboratory to be used
for exploring optimization algorithms in biological problems. This
platform is built on a blackboard-based agent architecture. As a test
case, the version of the platform presented here is devoted to the
study of protein folding, initially with a bead-like description of the
chain and with the widely used model of hydrophobic and polar
residues (HP model). Some details of the platform design are
presented along with its capabilities and also are revised some
explorations of the protein folding problems with different types of
discrete space. It is also shown the capability of the platform to
incorporate specific tools for the structural analysis of the runs in
order to understand and improve the optimization process.
Accordingly, the results obtained demonstrate that the ensemble of
computational tools into a single platform is worthwhile by itself,
since experiments developed on it can be designed to fulfill different
levels of information in a self-consistent fashion. By now, it is being
explored how an experiment design can be useful to create a
computational agent to be included within the platform. These
inclusions of designed agents –or software pieces– are useful for the
better accomplishment of the tasks to be developed by the platform.
Clearly, while the number of agents increases the new version of the
virtual laboratory thus enhances in robustness and functionality.