Prediction of Disordered Linkers Using APOD.

Intrinsically disordered linkers (DLs) connect protein domains and structural elements within domains and facilitate allosteric regulation. Computational studies suggest that thousands of proteins have DLs. Since there are only about 250 proteins with manually curated DL annotations (DisProt database ver. 9.3), computational approaches that make accurate predictions of DLs from the protein sequences are essential for reducing this annotation gap. To this end, we recently released the Accurate Predictor Of DLs (APOD) method. Empirical tests show that APOD achieves Area Under the ROC Curve (AUC) of 0.82 and Matthews Correlation Coefficient (MCC) of 0.42 on a low-similarity test dataset. We implement APOD as a freely available and convenient web server at https://yanglab.qd.sdu.edu.cn/APOD/ . This web server takes a protein sequence as the input and outputs an easy-to-parse prediction result, with the entire prediction process done on the server side. We also provide a standalone version of APOD for users who want to process large datasets of sequences. This version must be installed and run locally on the end user's computer. In this chapter, we overview APOD, explain how to locate and use the web server and the standalone implementation, and discuss how to read and interpret APOD's outputs. We also demonstrate utility of APOD based on a case study protein.