(178t) Modeling Nonspecific Interactions in Biology

Stealth materials, which resist nonspecific protein adsorption, are critical for biomedical and engineering applications. Such materials are able to provide a "clean background" onto which no bio-macromolecules can adhere. Modeling and designing such materials requires an understanding of their nonspecific interactions. Nonspecific interactions, low activity for many targets, are much less studied than specific interactions, high activity for a single target. Yet nonspecific interactions are essential for designing stealth materials. We've used modeling and bioinformatics techniques to mimic and understand how nature minimizes nonspecific interactions. Two systems in biology were targeted: the chemistry of protein surfaces and the chemistry of the interior of molecular chaperones. Both protein and molecular chaperone surfaces contact hundreds of protein types without aggregation and remain stable. Structures from thousands of proteins were stored in a relational database and various structural statistical methods were applied to gain insight into the patterns of surface residues and to find the differences between proteins from different ontological groups (protein location, organism source, etc.). We found that certain charged residues are common on the surface of proteins in more crowded environments and dominate the interior of molecular chaperones. The chaperone proteins were analyzed using simple probability models describing protein folding, from which charged and amide residues were shown to contribute the most towards stabilizing proteins, the function of molecular chaperones. Atomistic simulations were used to look deeper into the interactions between charged residues and their hydration. Experiments were conducted and confirmed that these modeling results lead to stealth materials.