Understanding the bioluminescence process of the chromophore in protein environment requires a reliable QM/MM model to accurately map the excited state potential energy surface. While high-level ab initio calculations have been applied to study the spectroscopic properties of the coelenteramide emitter in the absence of protein environment, their application to studying RLuc8 with various protonation state of the emitter requires immense computational resources. A pragmatic approach is using a QM/MM variant of the semiempirical QCFF/PI method developed in our group, which we utilized in our prior studies. For our current study, we leveraged the QCFF/PI quantum mechanical potential surface combined with the protein force field of the ENZYMIX program interfaced in the MOLARIS-XG software suite. Our previous studies have shown the success of this method, which integrates ENZYMIX and QCFF/PI, to investigate conjugated molecules in solutions or in the presence of protein environment.