期刊名称：Computational and Structural Biotechnology Journal
印刷版ISSN：2001-0370
出版年度：2021
卷号：19
页码：2750-2760
DOI：10.1016/j.csbj.2021.04.047
出版社：Computational and Structural Biotechnology Journal
摘要：Conformational stability of a protein is usually obtained by spectroscopically measuring the unfolding melting temperature. However, optical spectra under native conditions are considered to contain too little resolution to probe protein stability. Here, we have built and trained a neural network model to take the temperature-dependence of intrinsic fluorescence emission under native-only conditions as inputs, and then predict the spectra at the unfolding transition and denatured state. Application to a therapeutic antibody fragment demonstrates that thermal transitions obtained from the predicted spectra correlate highly with those measured experimentally. Crucially, this work reveals that the temperature-dependence of native fluorescence spectra contains a high-degree of previously hidden information relating native ensemble features to stability. This could lead to rapid screening of therapeutic protein variants and formulations based on spectroscopic measurements under non-denaturing temperatures only.
