PhosAF: An integrated deep learning architecture for predicting protein phosphorylation sites with AlphaFold2 predicted structures

Anal Biochem. 2024 Mar 19:115510. doi: 10.1016/j.ab.2024.115510. Online ahead of print.ABSTRACTPhosphorylation is indispensable in comprehending biological processes, while biological experimental methods for identifying phosphorylation sites are tedious and arduous. With the rapid growth of biotechnology, deep learning methods have made significant progress in site prediction tasks. Nevertheless, most existing predictors only consider protein sequence information, that limits the capture of protein spatial information. Building upon the latest advancement in protein structure prediction by AlphaFold2, a novel integrated deep learning architecture PhosAF is developed to predict phosphorylation sites in human proteins by integrating CMA-Net and MFC-Net, which considers sequence and structure information predicted by AlphaFold2. Here, CMA-Net module is composed of multiple convolutional neural network layers and multi-head attention is appended to obtaining the local and long-term dependencies of sequence features. Meanwhile, the MFC-Net module composed of deep neural network layers is used to capture the complex representations of evolutionary and structure features. Furthermore, different features are combined to predict the final phosphorylation sites. In addition, we put forward a new strategy to construct reliable negative samples via protein secondary structures. Experimental results on independent test data and case study indicate that our model PhosAF surpasses the curr...
Source: Analytical Biochemistry - Category: Biochemistry Authors: Source Type: research