(3cw) Modeling and Experiments of Nonspecific Interactions

Many of the difficulties of practical surface coatings and materials arise from the complexities of multiple interactions in biological environments. These interactions can be broadly broken into two categories: those which are important to function, high activity for a specific target, and nonspecific binding detrimental to function, low activity binding to many targets. These nonspecific interactions are central to many failures of drugs, sensors, and surface coatings in the harsh biological environments. Despite this fact, there is little modeling work on studying nonspecific interactions. Modeling all possible interactions within a such a system is difficult, yet there are ways to both indirectly study nonspecific binding and directly study many possible interactions using data-mining approaches. In this work, we describe recent work using bioinformatics, phenomenological modeling, molecular simulations, and experiments to study three types of nonspecific interactions. They are the weak nonspecific interactions between proteins in crowded environments, irreversible nonspecific protein adsorption onto surfaces, and nonspecific stabilization of proteins in molecular chaperones. These disparate systems have allowed us to generalize our conclusions into a small set of principles that other researchers should consider when designing specific activity in order to maintain resistance to nonspecific interactions.