The financial crisis that began in 2007 affected a number of funding markets, among them the secured and the unsecured interbank money markets. The phase after the collapse of Lehman Brothers in September 2008, in particular, was marked by a considerable loss in counterparty confidence. According to market participants, this loss of confidence resulted in a shift from the unsecured to the secured market.
Previous efforts in designing protein binding interfaces have focused on altering binding specificities. These methods fall short, however, when applied to the design of novel binding sites due to difficulties in accurately modeling protein backbones. The goal of this project is to create dimers from monomeric proteins. We developed a special docking algorithm that positions the member protein subunits to a plausible configuration with respect to each other using parameters determined from known complex structures. The docking procedure treats the proteins as rigid bodies and uses Fourier correlation theorem and fast Fourier transform to efficiently search for dimers with the highest interfacial surface complementarities. Using the docked structures as scaffolds for design and employing hydrophobic surface residues to drive dimer formation, we have demonstrated two successful designs, one heterodimer and one homodimer, using protein G and engrailed homeodomain respectively as the starting monomeric proteins. The designed dimers were characterized using circular dichroism, nuclear magnetic resonance, analytical ultracentrifugation, and X-ray crystallography methods. This is the first report of computationally designed de novo protein homodimers generated using a combination of protein docking and protein design tools. These results suggest that this strategy can be used to address the protein recognition problem, and is generally applicable to creating novel binding sites with compatible binding partners
The focus of this report (and its companion) is on the key economic effects of problems associated with housing affordability. The basic aim is to provide a broader than normal rationale for, and a basis on which to develop, policies designed to improve affordability outcomes. Housing affordability is here considered in relation to the operation of the national and regional economies and not merely as a question of social policy.
The traditional theory of public finance identifies three fields or ‘branches’ of economic intervention by the state allocation, distribution and stabilisation (Musgrave, 1959). In the first place governments may intervene to of fset or correct market imperfections and failures. Secondly, governments act to change the market determined distribution of income and wealth. Finally, since the mid twentieth centuries, governments and key agencies like central banks, have taken on the responsibility of steering the whole economy to achieve some combination of price stability, adequate aggregate employment and external economic balance.
