在这项研究中，研究者以人工合成荧光素DTZ（diphenylterazine）作为研究的催化底物（图3），因为它具有高量子产率、红移发射、有利的体内药代动力学以及发光无需辅因子等特点。
此前，David Baker组曾报道了一系列从序列-结构关系出发的蛋白质设计相关算法（图4）。“Hallucination”方法指在序列空间中进行采样，使用神经网络来优化，从而产生有意义结构的序列，这项方法保证了序列的多样性；“Rosetta sequence-design approaches” 则是从目标结构出发，生成符合该结构的氨基酸序列，从而保证了结构的特异性；而trRosetta用来做结构预测。
-023-05696-3
2. Anishchenko, I., Pellock, S. J., Chidyausiku, T. M., Ramelot, T. A., Ovchinnikov, S., Hao, J., Bafna, K., Norn, C., Kang, A., Bera, A. K., DiMaio, F., Carter, L., Chow, C. M., Montelione, G. T., & Baker, D. (2021). De novo protein design by deep network hallucination. Nature, 600(7889), 547–552.
https://doi.org/10.1038/s41586-021-04184-w
3. Cao, L., Coventry, B., Goreshnik, I., Huang, B., Sheffler, W., Park, J. S., Jude, K. M., Marković, I., Kadam, R. U., Verschueren, K. H. G., Verstraete, K., Walsh, S. T. R., Bennett, N., Phal, A., Yang, A., Kozodoy, L., DeWitt, M., Picton, L., Miller, L., Strauch, E. M., … Baker, D. (2022). Design of protein-binding proteins from the target structure alone. Nature, 605(7910), 551–560. https://doi.org/10.1038/s41586-022-04654-9
4. Norn, C., Wicky, B. I. M., Juergens, D., Liu, S., Kim, D., Tischer, D., Koepnick, B., Anishchenko, I., Foldit Players, Baker, D., & Ovchinnikov, S. (2021). Protein sequence design by conformational landscape optimization. Proceedings of the National Academy of Sciences of the United States of America, 118(11), e2017228118.
https://doi.org/10.1073/pnas.2017228118
5. Yang, J., Anishchenko, I., Park, H., Peng, Z., Ovchinnikov, S., & Baker, D. (2020). Improved protein structure prediction using predicted interresidue orientations. Proceedings of the National Academy of Sciences of the United States of America, 117(3), 1496–1503. https://doi.org/10.1073/pnas.1914677117
来源：北京生物结构前沿研究中心
评论 (0)