Ultrahigh molecular recognition specificity of competing DNA oligonucleotide strands in thermal equilibrium: a cooperative transition to order

摘要

The specificity of molecular recognition is important to molecularself-organization. A prominent example is the biological cell where, within ahighly crowded molecular environment, a myriad of different molecular receptorpairs recognize their binding partner with astonishing accuracy. In thermalequilibrium it is usually admitted that the affinity of recognizer pairs onlydepends on the nature of the two binding molecules. Accordingly, Boltzmannfactors of binding energy differences relate the molecular affinities amongdifferent target molecules that compete for the same probe. Here, we considerthe molecular recognition of short DNA oligonucleotide single strands. We showthat a better matching oligonucleotide strand can prevail against adisproportionally more concentrated competitor that exhibits reduced affinitydue to a mismatch. The magnitude of deviation from the simple picture above mayreach several orders of magnitude. In our experiments the effective molecularaffinity of a given strand remains elevated only as long as the better matchingcompetitor is not present. We interpret our observations based on anenergy-barrier of entropic origin that occurs if two competing oligonucleotidestrands occupy the same probe simultaneously. In this situation the relativebinding affinities are reduced asymmetrically, which leads to an expression ofthe free energy landscape that represents a formal analogue of a Landaudescription of phase transitions. Our mean field description reproduces theobservations in quantitative agreement. The advantage of improved molecularrecognition comes at no energetic cost other than the design of the molecularensemble, and the introduction of the competitor. It will be interesting to seeif mechanisms along similar lines as exposed here, contribute to the molecularsynergy that occurs in biological systems.