The third lecture gave an insight into the molecular aspects of information transmission more relevant than what happens in cells. Error in molecular recognition is inevitable due to finite and often small differences in binding energies between competing molecules, whether nucleic acids coupled to their complements, signaling molecules binding to receptors or, generally, substrates binding to enzymes. However, the error can be reduced, at least arbitrarily, by expending energy in the classic proofreading process. Replay can be based on kinetic discrimination dominated by differences between the energy barriers to binding, or energetic discrimination dominated by differences between the free energy of the bound states.
Beyond the problem of precision, the conference focused on traditional approaches to reasoning about cellular decision making. These approaches dramatically reduce Combinatorics complexity by using an arsenal of schemes of small chemical reaction networks, modeled with kinetic equations, to implement a repertoire of basic behaviors. A review of significant schemes begins by establishing an equilibrium bond, whose saturation behavior underlies the tunable reaction order in the classical model of enzyme-substrate interactions. Single bonding has been generalized to multivalent bonding, which, when sequential, leads to threshold behavior. A scenario in which both enzyme and substrate must bind to a scaffold before they can interact leads to signal transmission when the scaffold is present in low concentration, but leads to ligand isolation when the scaffold concentration is high.
In general, circuits based on equilibrium binding can implement a variety of logical propositions. Perhaps the most elementary unit of construction outside equilibrium is the make/unmake (Goldbeter-Koshland) loop, which, depending on operating conditions, can provide ultra-sensitive on/off behavior or an elementary form of precise adaptation. Combining such loops in series in a cascade can produce amplification, and combining them in parallel leads to a threshold. Adding the feedbacks together leads to hysteresis and, therefore, memory. Taken together, these and other patterns generate something resembling a " programming language " of primitive behaviors that can be combined and nested into signaling circuits of great complexity.
