The development of DCC-based sensors remains a broadly applicable endeavor within the field of supramolecular chemistry. However, the identification and deconvolution of subtle NCIs that are important to sensor performance remains an unsolved problem. In this study, we used a combination of computational parameterization, statistical modeling, and high-level DFT calculations to develop and gain a detailed understanding of the first reported chiroptical sensor for g-stereogenic alcohols. By performing two iterations of a data-driven optimization workflow, we were able to identify a highly effective sensor and produce a robust, interpretable statistical model. This provided the basis to deconvolute the roles of distal and proximal steric bulk on sensor performance by mathematically relating the distance resolved sterimol parameters Bmax 2 Å and Bmax 8.5 Å to CD-signal intensity. We then performed high-level DFT calculations to understand the physical significance of the steric parameters. These calculations both revealed a likely sensing mechanism and suggested that both distal and proximal substituents influence sensor performance through attractive NCIs. This work demonstrates the effectiveness of an iterative data-driven approach to sensor design and showcases the utility of computational parameterization and statistical modeling to deconvolute competing weak NCIs. We anticipate that the workflows described herein can be readily adopted for the design of other DCC-based assemblies and in the design and understanding of new supramolecular systems at large. It should be noted that 13i and 13j were not chosen using the workflow outlined in Figure . For further discussion see the SI. McInnes, L.; Healy, J.; Saul, N.; Großberger, L. UMAP: Uniform Manifold Approximation and Projection. J. Open Source Softw. 2018, 3, 861. It should be noted that both enantiomers of alcohol 11b were tested in several assemblies. As expected, equal and opposite Cotton effects were observed (see SI for more details). This Cotton effect lmax deviated by ± 2 nm at the most, however, it typically only deviated by ± 0.5 nm. All reported CD-signals were normalized by dividing the measured CD-signal (mdeg) by the absorbance. Our group has extensively employed DFT-parameterization followed by multivariate linear regression for reaction development. For further discussion see references 28-30. It should be noted that assembly 12ca was an outlier and was not included in model development. It is likely that the nitroaromatic moiety engages in distinct p-p NCIs with the g-phenyl ring of 11a that are not accounted for by our models. For further information about parameter collection, see discussion in the SI. As in the modeling depicted in Figure , assembly 12ca was an outlier and was excluded from model development. Luchini, G.; Paton, R. S. DBSTEP: DFT Based Steric Parameters. 2021, DOI: 10.5281/zenodo.4702097. It should be noted that Paton's advanced distance-resolved sterimol descriptors were critically important as the simple sterimol measurements of the arene as a whole were poorly correlated to CD signal. The opposite correlations for proximal and distal encumbrance likely counteract one another when distance-resolved parameters are not used. The dr of assemblies 12 was conveniently measured by integrating the aminal methine proton, who's signal was well-resolved for almost all assemblies observed. The assemblies that did not feature two clear, well-resolved methine signals for the two diastereomers were not included in the plot. It should be noted that dr measurements were conducted using racemic 11a due to cost considerations.