Despite the growing list of analytes for which SWCNT-based sensors have been developed, the mechanisms behind their molecular recognition and optical modulation remain poorly understood. In this work, we studied (GT)6-SWCNT bio-nano hybrids, which exhibit vigorous fluorescence modulation when exposed to catecholamines, a family of biologically important small molecules. Our goal was to enhance the understanding of sensor optical modulation by systematically exploring the relationship between ligand properties and optical responses. We complemented our experimental findings with MD simulations to rationalize our experimental observations and gain valuable insights.