Real-time structure search and structure classification for AlphaFold protein models.

Last year saw a breakthrough in protein structure prediction, where the AlphaFold2 method showed a substantial improvement in the modeling accuracy. Following the software release of AlphaFold2, predicted structures by AlphaFold2 for proteins in 21 species were made publicly available via the AlphaFold Database. Here, to facilitate structural analysis and application of AlphaFold2 models, we provide the infrastructure, 3D-AF-Surfer, which allows real-time structure-based search for the AlphaFold2 models. In 3D-AF-Surfer, structures are represented with 3D Zernike descriptors (3DZD), which is a rotationally invariant, mathematical representation of 3D shapes. We developed a neural network that takes 3DZDs of proteins as input and retrieves proteins of the same fold more accurately than direct comparison of 3DZDs. Using 3D-AF-Surfer, we report structure classifications of AlphaFold2 models and discuss the correlation between confidence levels of AlphaFold2 models and intrinsic disordered regions.

Koch's Tuberculosis of the Sternoclavicular Joint.

Introduction: Tuberculosis bacilli have lived in symbiosis with mankind since time memorial. Rigveda and Atharvaveda (3500-188 B.C), Samhita of charka and Sushruta (1000 and 600 B.C) have mentioned the disease by the name of "Yakshma" in all forms. Lesions have been found in Egyptian mummies also. In western world, the clinical features and communicability of the disease were known before 1000 B.C. Tuberculosis is still a challenging health problem in developing countries, affecting almost all organs. Osteo articular tuberculosis is uncommon. Tuberculosis involving the sternoclavicular joint is extremely rare and often is misdiagnosed because of its rarity and unusual location. Literature has very less number of cases reported so far. Case Presentation: We are hereby reporting the case of a 70-year-old male, carpenter by profession who presented with right sternoclavicular joint swelling. Magnetic resonance imaging showed synovial thickening, articular, and subarticular erosions with diffuse sub chondral edema. Diagnosis was confirmed by ZN staining, FNAC, and diagnostic biopsy. Patient was managed conservatively by anti-tubercular treatment. Follow-up showed no relapse and improved clinical symptoms. Conclusion: Earlier detection and management of tuberculosis of such rare variants of joint infection help in preventing the destruction of osteo ligamentous structures, abscess formation, and joint instability. The report emphasizes on the appropriate diagnosis and management.

LZerD Protein-Protein Docking Webserver Enhanced With de novo Structure Prediction.

Protein-protein docking is a useful tool for modeling the structures of protein complexes that have yet to be experimentally determined. Understanding the structures of protein complexes is a key component for formulating hypotheses in biophysics regarding the functional mechanisms of complexes. Protein-protein docking is an established technique for cases where the structures of the subunits have been determined. While the number of known structures deposited in the Protein Data Bank is increasing, there are still many cases where the structures of individual proteins that users want to dock are not determined yet. Here, we have integrated the AttentiveDist method for protein structure prediction into our LZerD webserver for protein-protein docking, which enables users to simply submit protein sequences and obtain full-complex atomic models, without having to supply any structure themselves. We have further extended the LZerD docking interface with a symmetrical homodimer mode. The LZerD server is available at https://lzerd.kiharalab.org/.

LZerD webserver for pairwise and multiple protein-protein docking.

Protein complexes are involved in many important processes in living cells. To understand the mechanisms of these processes, it is necessary to solve the 3D structures of the protein complexes. When protein complex structures have not yet been determined by experiment, protein-protein docking tools can be used to computationally model the structures of these complexes. Here, we present a webserver which provides access to LZerD and Multi-LZerD protein docking tools. The protocol provided by the server have performed consistently among the top in the CAPRI blind evaluation. LZerD docks pairs of structures, while Multi-LZerD can dock three or more structures simultaneously. LZerD uses a soft protein surface representation with 3D Zernike descriptors and explores the binding pose space using geometric hashing. Multi-LZerD performs multi-chain docking by combining pairwise solutions by LZerD. Both methods output full-atom docked models of the input proteins. Users can also input distance constraints between interacting or non-interacting residues as well as residues that locate at the interface or far from the interface. The webserver is equipped with a user-friendly panel that visualizes the distribution and structures of binding poses of top scoring models. The LZerD webserver is available at https://lzerd.kiharalab.org.