No abstract

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.

The novel coronavirus (SARS-CoV-2) has caused a global pandemic, which can cause cough, fever, muscle aches, fatigue and, sore throat. However, most people do not know how to cope with them so that some patients may progress to pneumonia and even severe disease. Therefore, it’s crucial to effectively cope with COVID-19 infection at home to reduce the rate of hospitalization, ease the burden of healthcare systems, alleviate patients’ suffering, and shorten the illness duration. In this regard, we aim to describe the symptom groups of the recently epidemic BF.7 variant strain infection, and summarize previous clinical experience and expert guidelines, the following home care measures for the five main symptoms were proposed. We hope that these strategies will serve as a reference for home care of patients and help them take appropriate measures to manage their symptoms.