As computational techniques have grown in speed and accuracy, the interplay of experiment and computation has become an attractive way to tackle chemical problems. Our research group has been particularly interested in combining experimental and computational efforts to elucidate reaction mechanisms, predict reaction outcomes, and design new molecules. Molecular design of chemical tools has a broad range of applications, from the development of probes for use in chemical and cell biology to the development of chiral catalysts for use in enantioselective chemical synthesis. This thesis spans this range of applications, demonstrating how experimental and computational studies can inspire and inform one another. This interplay is first shown in the design, synthesis, and evaluation of a novel 15-azasterol as a luminescent cholesterol mimic for the monitoring of cholesterol trafficking. The brightness of this probe, which is ~32 times greater than the widely used dehydroergosterol (DHE) probe, is combined with resistance to photobleaching in solution and in human fibroblasts and an exceptionally large Stokes-like shift of ~150-200 nm. The experimental observations of the probe motivated computational studies to explain the photophysical properties and predict protein binding behavior. The study of this cholesterol mimic also prompted the design and synthesis of other luminescent steroid mimics, which are described herein. The interplay of experiment and computation is also shown in work on the prediction of enantioselectivity for catalyst screening and design of chiral ligands. The quantum-guided molecular mechanics (Q2MM) method is used to develop transition state force fields (TSFFs) that enable conformational sampling of transition state structures, which allows for accurate prediction of enantioselectivity to aid in selection of known catalysts. This thesis reports efforts toward the development of TSFF parameters for the asymmetric transfer hydrogenation (ATH) of ketones using half-sandwich complexes of Ru, Rh, and Ir. It also describes a new application of Q2MM and TSFFs in the in silico design of novel ligand classes, enabling a user to virtually screen new ligand designs prior to synthesis. The design of chiral ligands with predicted enantioselectivities up to 97.9% ee for ATH reduction of acetophenone and efforts toward their synthesis are reported herein.