Residual dipolar couplings (RDCs) provide important constraints for the determination and refinement of protein NMR structures. Based on echo-anti-echo manipulation or IPAP principle, a suite of sensitivity enhanced experiments are described for measuring backbone ¹H^N−¹⁵N, ¹⁵N−¹³C′, ¹H^N−¹³C′, ¹³C′−¹³C^α, ¹³C^α−¹H^α, ^15N(i)−¹³C^α(i), ¹H^N(i)−^13α(i), ¹⁵N(i)−¹³C^α(i −1), and ¹H^N(i)−¹³C^α(i − 1) dipolar couplings in proteins. The accuracy of the measured couplings can be assessed by comparing the experimentally obtained values with those predicted based on high resolution structures. Even forverysmall RDCs, such as the ¹⁵N(i)−¹³C^α(i − 1) couplings that are smaller than 0.3 Hz, a correlation coefficient of 0.83 is obtained, attesting to the accuracy of couplings obtained with these sensitivity-enhanced IPAP experiments. We also present a novel application for the use of RDCs. Under certain conditions, the folded state of aprotein comprises detectable, conformational sub-states. Such sub-states at local sites, so-called melting hot spots, are characterized by re-orienting bond vectors. Determination of RDCs allows for efficient and easy detection of such hot spots.