Fluorescent protein (FP) variants have recently emerged as promising intracellular nitric oxide (NO) sensors based on NO-induced fluorescence loss due to cysteine S-nitrosylation - the covalent addition of a nitroso group to a cysteine thiol within a protein to form an S-nitrosothiol. Here, we investigate the mechanisms underlying this fluorescence loss using a combined experimental and computational approach. We focus on mTagBFP2, a blue fluorescent protein that undergoes a 70% reduction in flu