Quantitative spectral comparison by weighted spectral difference for protein higher order structure confirmation.

Previously, different approaches of spectral comparison were evaluated, and the spectral difference (SD) method was shown to be valuable for its linearity with spectral changes and its independence on data spacing (Anal. Biochem. 434 (2013) 153-165). In this note, we present an enhancement of the SD calculation, referred to as the "weighted spectral difference" (WSD), by implementing a weighting function based on relative signal magnitude. While maintaining the advantages of the SD method, WSD improves the method sensitivity to spectral changes and tolerance for baseline inclusion. Furthermore, a generalized formula is presented to unify further development of approaches to quantify spectral difference.