Characterization of the phenolate-keto oxyluciferin/luciferase interactions in the S1 state by QM/MM energy decomposition analysis

Unraveling the nature of the interaction on the complex formed by the oxyluciferin chromophore in the first electronically excited state and the luciferase enzyme can lead to a more profound understanding of fireflies’ bioluminescence, which is a natural process with a large amount of applications i...

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Detalles Bibliográficos
Autores: Mateo de la Fuente, Henar, Anguita Ortiz, Nuria, Mandado, Marcos, Nogueira Pérez, Juan José
Tipo de recurso: artículo
Fecha de publicación:2026
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:dnet:biblosearchi::2d6dd366d184a039bf09115e0357bb13
Acceso en línea:https://hdl.handle.net/10486/775001
https://dx.doi.org/10.1016/j.compbiolchem.2026.109148
Access Level:acceso abierto
Palabra clave:Bioluminescence
Luciferin
Energy-decomposition analysis
QM/MM
Molecular dynamics
Química
Descripción
Sumario:Unraveling the nature of the interaction on the complex formed by the oxyluciferin chromophore in the first electronically excited state and the luciferase enzyme can lead to a more profound understanding of fireflies’ bioluminescence, which is a natural process with a large amount of applications in medicine. In this work, we have studied the interaction of the phenolate-keto oxyluciferin (OLU) chromophore and the luciferase protein, and we have found that the interaction energy is governed mostly by electrostatic terms. Nonetheless, non-electrostatic contributions are non-negligible due to the high presence of -systemcontaining amino acids within the bioluminescent pocket. Furthermore, we have outlined a methodology for performing energy decomposition analysis in the excited state using a multiscale hybrid electrostaticembedding QM/MM approach, stressing that the OLUFF force field is not suitable for this task from a force field-base approach. Moreover, we have analyzed how the proximity of PHE249 and SER349 affect the different terms of the interaction energy, unraveling that the most relevant terms of their contributions are polarization and electrostatic, respectively. This strategy can be extended to investigate the interactions of the other three potential emitters within the OLU/luciferase complex, as well as complexes with mutated proteins. Such analyses may help clarify the factors governing color modulation in the bioluminescent process and provide valuable insights for tuning the OLU/luciferase complex to enhance its applicability