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It is often assumed in the field of QSAR that models cannot produce predictions which are more accurate than their training data. Additionally, it is implicitly assumed, by necessity, that data points in test sets or validation sets do not contain error, and that each data point is a population mean. This work proposes the hypothesis that QSAR models\n                    <jats:italic>can<\/jats:italic>\n                    make predictions which are more accurate than their training data and that the error-free test set assumption leads to a significant misevaluation of model performance. This work used 8 datasets with six different common QSAR endpoints, because different endpoints should have different amounts of experimental error associated with varying complexity of the measurements. Up to 15 levels of simulated Gaussian distributed random error was added to the datasets, and models were built on the error laden datasets using five different algorithms. The models were trained on the error laden data, evaluated on\n                    <jats:italic>error-laden<\/jats:italic>\n                    test sets, and evaluated on\n                    <jats:italic>error-free<\/jats:italic>\n                    test sets. The results show that for each level of added error, the RMSE for evaluation on the error free test sets was always better. The results support the hypothesis that, at least under the conditions of Gaussian distributed random error, QSAR models can make predictions which are more accurate than their training data, and that the evaluation of models on error laden test and validation sets may give a flawed measure of model performance. These results have implications for how QSAR models are evaluated, especially for disciplines where experimental error is very large, such as in computational toxicology.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1186\/s13321-021-00571-7","type":"journal-article","created":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T07:03:08Z","timestamp":1637823788000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["The effect of noise on the predictive limit of QSAR models"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7797-700X","authenticated-orcid":false,"given":"Scott S.","family":"Kolmar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Grulke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,25]]},"reference":[{"issue":"4","key":"571_CR1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S1093-3263(01)00123-1","volume":"20","author":"A Golbraikh","year":"2002","unstructured":"Golbraikh A, Tropsha A (2002) Beware of q2! 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