Compositions and methods for highly specific nucleic acid probes and primers are provided. The probe system comprises a complement strand and a protector stand that form a partially double-stranded probe. The reaction standard free energy of hybridization between the probe and target nucleic acid as determined by Expression 1 (ΔG°rxn=ΔG°t-TC−ΔG°nh-PC+(ΔG°v-TC−ΔG°h-PC)) is from about −4 kcal/mol to about +4 kcal/mol. Alternatively, the reaction standard free energy of hybridization between the probe and target nucleic acid is determined by Expression 1 to be within 5 kcal/mol of the standard free energy as determined by Expression 2 (−Rτ ln(([P]0−[C]0)/[C]0)]), where the [P]0 term of Expression 2 equals the concentration of the protector strand and the [C]0 term of Expression 2 equals the concentration of the complement strand. In addition, a method for on-the-fly fine tuning of a reaction using the present probe is provided.