The specificity of molecular recognition is important for molecular self-organization. A prominent example is the biological cell where a myriad of different molecular receptor pairs recognize their binding partners with astonishing accuracy within a highly crowded molecular environment. In thermal equilibrium it is usually admitted that the affinity of recognizer pairs only depends on the nature of the two binding molecules. Accordingly, Boltzmann factors of binding energy differences relate the molecular affinities among different target molecules that compete for the same probe. Here, we consider the molecular recognition of short DNA oligonucleotide single strands. We show that a better matching oligonucleotide can prevail against a disproportionally more concentrated competitor with reduced affinity due to a mismatch. We investigate the situation using fluorescence-based techniques, among them Frster resonance energy transfer and total internal reflection fluorescence excitation. We find that the affinity of certain strands appears considerably reduced only as long as a better matching competitor is present. Compared to the simple Boltzmann picture above we observe increased specificity, up to several orders of magnitude. We interpret our observations based on an energy-barrier of entropic origin that occurs if two competing oligonucleotide strands occupy the same probe simultaneously. Due to their differences in binding microstate distributions, the barrier affects the binding affinities of the competitors differently. Based on a mean field description, we derive a resulting expression for the free energy landscape, a formal analogue to a Landau description of phase transitions reproducing the observations in quantitative agreement as a result of a cooperative transition. The advantage of improved molecular recognition comes at no energetic cost other than the design of the molecular ensemble and the presence of the competitor. As a possible application, binding assays for the detection of single nucleotide polymorphisms in DNA strands could be improved by adding competing strands. It will be interesting to see if mechanisms along similar lines as exposed here contribute to the molecular synergy that occurs in biological systems.

分子识别的特异性对于分子自组织具有重要意义。一个突出的例子是生物细胞，其中无数不同的分子受体对在高度拥挤的分子环境中以惊人的准确性识别它们的结合伙伴。在热平衡中，通常承认识别器对的亲和力仅取决于两个结合分子的性质。因此，结合能差异的玻尔兹曼因子与竞争相同探针的不同靶分子之间的分子亲和力有关。在这里，我们考虑短 DNA 寡核苷酸单链的分子识别。我们表明，更好匹配的寡核苷酸可以胜过由于错配而导致亲和力降低的不成比例地更集中的竞争者。我们使用基于荧光的技术研究这种情况，其中包括 Frster 共振能量转移和全内反射荧光激发。我们发现，只有存在更好匹配的竞争对手时，某些链的亲和力才会显着降低。与上面的简单玻尔兹曼图相比，我们观察到特异性提高了几个数量级。我们根据熵起源的能量屏障来解释我们的观察结果，如果两条竞争的寡核苷酸链同时占据同一探针，则会发生这种能量屏障。由于它们在结合微状态分布方面的差异，屏障对竞争者的结合亲和力的影响不同。基于平均场描述，我们推导出自由能景观的结果表达式，作为合作转变的结果，Landau 描述相变的形式类似，再现了定量一致的观察结果。除了分子集合的设计和竞争者的存在之外，改进分子识别的优势不在于能源成本。作为一种可能的应用，可以通过添加竞争链来改进用于检测 DNA 链中单核苷酸多态性的结合测定。看看这里所揭示的类似机制的机制是否有助于生物系统中发生的分子协同作用，这将是一件有趣的事情。除了分子集合的设计和竞争者的存在之外，改进分子识别的优势不在于能源成本。作为一种可能的应用，可以通过添加竞争链来改进用于检测 DNA 链中单核苷酸多态性的结合测定。看看这里所揭示的类似机制的机制是否有助于生物系统中发生的分子协同作用，这将是一件有趣的事情。除了分子集合的设计和竞争者的存在之外，改进分子识别的优势不在于能源成本。作为一种可能的应用，可以通过添加竞争链来改进用于检测 DNA 链中单核苷酸多态性的结合测定。看看这里所揭示的类似机制的机制是否有助于生物系统中发生的分子协同作用，这将是一件有趣的事情。