title: Illuminating the origins of spectral properties of green fluorescent proteins via proteochemometric and molecular modeling.
abstract: Green fluorescent protein (GFP) has immense utility in biomedical imaging owing to its autofluorescent nature. In efforts to broaden the spectral diversity of GFP, there have been several reports of engineered mutants via rational design and random mutagenesis. Understanding the origins of spectral properties of GFP could be achieved by means of investigating its structure-activity relationship. The first quantitative structure-property relationship study for modeling the spectral properties, particularly the excitation and emission maximas, of GFP was previously proposed by us some years ago in which quantum chemical descriptors were used for model development. However, such simplified model does not consider possible effects that neighboring amino acids have on the conjugated π-system of GFP chromophore. This study describes the development of a unified proteochemometric model in which the GFP chromophore and amino acids in its vicinity are both considered in the same model. The predictive performance of the model was verified by internal and external validation as well as Y-scrambling. Our strategy provides a general solution for elucidating the contribution that specific ligand and protein descriptors have on the investigated spectral property, which may be useful in engineering novel GFP variants with desired characteristics.
authors.affiliation: Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, 10700, Thailand; Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, 10700, Thailand.
authors.forename: Chanin
authors.initials: C
authors.lastname: Nantasenamat
authors.forename: Saw
authors.initials: S
authors.lastname: Simeon
authors.forename: Wiwat
authors.initials: W
authors.lastname: Owasirikul
authors.forename: Napat
authors.initials: N
authors.lastname: Songtawee
authors.forename: Maris
authors.initials: M
authors.lastname: Lapins
authors.forename: Virapong
authors.initials: V
authors.lastname: Prachayasittikul
authors.forename: Jarl E S
authors.initials: JE
authors.lastname: Wikberg
mesh_terms: D000596:Amino Acids / Q000032:analysis / Q000737:chemistry*; D019295:Computational Biology; D049452:Green Fluorescent Proteins / Q000737:chemistry* / Q000235:genetics; D008024:Ligands; D008958:Models, Molecular; D015202:Protein Engineering; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D008024:Ligands; D049452:Green Fluorescent Proteins
keywords: chromophore; data mining; green fluorescent protein; molecular modeling; proteochemometrics