article published yes Louisa Gonzalez Somermeyer author 4720D23C-F248-11E8-B48F-1D18A9856A870000-0001-9139-5383 Aubin Fleiss author Alexander S Mishin author Nina G Bozhanova author Anna A Igolkina author Jens Meiler author Maria-Elisenda Alaball Pujol author Ekaterina V Putintseva author Karen S Sarkisyan author Fyodor Kondrashov author 44FDEF62-F248-11E8-B48F-1D18A9856A870000-0001-8243-4694 GradSch department FyKo department Characterizing the fitness landscape on population and global scales project International IST Doctoral Program project Studies of protein fitness landscapes reveal biophysical constraints guiding protein evolution and empower prediction of functional proteins. However, generalisation of these findings is limited due to scarceness of systematic data on fitness landscapes of proteins with a defined evolutionary relationship. We characterized the fitness peaks of four orthologous fluorescent proteins with a broad range of sequence divergence. While two of the four studied fitness peaks were sharp, the other two were considerably flatter, being almost entirely free of epistatic interactions. Mutationally robust proteins, characterized by a flat fitness peak, were not optimal templates for machine-learning-driven protein design – instead, predictions were more accurate for fragile proteins with epistatic landscapes. Our work paves insights for practical application of fitness landscape heterogeneity in protein engineering. https://research-explorer.ista.ac.at/download/11448/11454/2022_eLife_Somermeyer.pdf application/pdfno eLife Sciences Publications2022 eng General Immunology and MicrobiologyGeneral BiochemistryGenetics and Molecular BiologyGeneral MedicineGeneral Neuroscience 2050-084X 35510622 00079919720000110.7554/elife.75842 11 https://research-explorer.ista.ac.at/record/17850 https://github.com/aequorea238/Orthologous_GFP_Fitness_Peaks L. Gonzalez Somermeyer, A. Fleiss, A.S. Mishin, N.G. Bozhanova, A.A. Igolkina, J. Meiler, M.-E. Alaball Pujol, E.V. Putintseva, K.S. Sarkisyan, F. Kondrashov, ELife 11 (2022). Gonzalez Somermeyer L, Fleiss A, Mishin AS, et al. Heterogeneity of the GFP fitness landscape and data-driven protein design. <i>eLife</i>. 2022;11. doi:<a href="https://doi.org/10.7554/elife.75842">10.7554/elife.75842</a> Gonzalez Somermeyer L, Fleiss A, Mishin AS, Bozhanova NG, Igolkina AA, Meiler J, Alaball Pujol M-E, Putintseva EV, Sarkisyan KS, Kondrashov F. 2022. Heterogeneity of the GFP fitness landscape and data-driven protein design. eLife. 11, 75842. L. Gonzalez Somermeyer <i>et al.</i>, “Heterogeneity of the GFP fitness landscape and data-driven protein design,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022. Gonzalez Somermeyer, L., Fleiss, A., Mishin, A. S., Bozhanova, N. G., Igolkina, A. A., Meiler, J., … Kondrashov, F. (2022). Heterogeneity of the GFP fitness landscape and data-driven protein design. <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/elife.75842">https://doi.org/10.7554/elife.75842</a> Gonzalez Somermeyer, Louisa, Aubin Fleiss, Alexander S Mishin, Nina G Bozhanova, Anna A Igolkina, Jens Meiler, Maria-Elisenda Alaball Pujol, Ekaterina V Putintseva, Karen S Sarkisyan, and Fyodor Kondrashov. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href="https://doi.org/10.7554/elife.75842">https://doi.org/10.7554/elife.75842</a>. Gonzalez Somermeyer, Louisa, et al. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” <i>ELife</i>, vol. 11, 75842, eLife Sciences Publications, 2022, doi:<a href="https://doi.org/10.7554/elife.75842">10.7554/elife.75842</a>. 114482022-06-18T09:06:59Z2026-10-02T11:21:40Z