Characterizing Protein-Protein Interactions with the Fragment Molecular Orbital Method

Proteins are vital components of living systems, serving as building blocks, molecular machines, enzymes, receptors, ion channels, sensors, and transporters. Protein-protein interactions (PPIs) are a key part of their function. There are more than 645,000 reported disease-relevant PPIs in the human interactome, but drugs have been developed for only 2% of these targets. The advances in PPI-focused drug discovery are highly dependent on the availability of structural data and accurate computational tools for analysis of this data. Quantum mechanical approaches are often too expensive computationally, but the fragment molecular orbital (FMO) method offers an excellent solution that combines accuracy, speed and the ability to reveal key interactions that would otherwise be hard to detect. FMO provides essential information for PPI drug discovery, namely, identification of key interactions formed between residues of two proteins, including their strength (in kcal/mol) and their chemical nature (electrostatic or hydrophobic). In this chapter, we have demonstrated how three different FMO-based approaches (pair interaction energy analysis (PIE analysis), subsystem analysis (SA) and analysis of protein residue networks (PRNs)) have been applied to study PPI in three protein-protein complexes

Terrestrial trophic dynamics in the Canadian Arctic

The Swedish Tundra Northwest Expedition of 1999 visited 17 sites throughout the Canadian Arctic. At 12 sites that were intensively sampled we estimated the standing crop of plants and the densities of herbivores and predators with an array of trapping, visual surveys, and faecal-pellet transects. We developed a trophic-balance model using ECOPATH to integrate these observations and determine the fate of primary and secondary production in these tundra ecosystems, which spanned an 8-fold range of standing crop of plants. We estimated that about 13% of net primary production was consumed by herbivores, while over 70% of small-herbivore production was estimated to flow to predators. Only 9% of large-herbivore production was consumed by predators. Organization of Canadian Arctic ecosystems appears to be more top-down than bottom-up. Net primary production does not seem to be herbivore-limited at any site. This is the first attempt to integrate trophic dynamics over the entire Canadian Arctic