Intrinsically disordered proteins (IDPs) account for more than 50% of the human proteome and are closely associated with tumors, cardiovascular diseases, and neurodegeneration, which have no fixed three-dimensional structure under physiological conditions. Due to the characteristic of conformational diversity, conventional experimental methods of structural biology, such as NMR, X-ray diffraction, and CryoEM, are unable to capture conformational ensembles. Molecular dynamics (MD) simulation can sample the dynamic conformations at the atomic level, which has become an effective method for studying the structure and function of IDPs. However, the high computational cost prevents MD simulations from being widely used for IDPs conformational sampling. In recent years, significant progress has been made in artificial intelligence, which makes it possible to solve the conformational reconstruction problem of IDP with fewer computational resources. Here, based on short MD simulations of different IDPs systems, we use variational autoencoders (VAEs) to achieve the generative reconstruction of IDPs structures and include a wider range of sampled conformations from longer simulations. Compared with the generative autoencoder (AEs), VAEs add an inference layer between the encoder and decoder in the latent space, which can cover the conformational landscape of IDPs more comprehensively and achieve the effect of enhanced sampling. Through experimental verification, the Cα RMSD between VAE-generated and MD simulation sampling conformations in the 5 IDPs test systems was significantly lower than that of AE. The Spearman correlation coefficient on the structure was higher than that of AE. VAE can also achieve excellent performance regarding structured proteins. In summary, VAEs can be used to effectively sample protein structures.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.