The problem arises when only one or a small group of conformations show strong interactions with the protein, which is often the typical case. If the docking scoring functions inaccurately estimate higher intramolecular energies, these results will be ranked lower on the hit list, and the docking will miss that drug molecule, leading to a false negative. Similarly, when conformations that show strong interactions with the protein are deemed energetically feasible by the scoring function, but in reality, they are not due to large conformational strain energies that the scoring function fails to estimate correctly, these false positives fill the top of the hit list, pushing down the true positives. Unfortunately, these two issues tend to occur together. Introducing a relatively flat intramolecular model scoring function, where the conformational strain energies are smaller in magnitude than the protein-ligand intermolecular interactions, could reduce the number of false negatives but would simultaneously increase the number of false positives, leading to no overall improvement in outcome.