Dear CCP4, We are pleased to invite you to the next DRIIMB Webinar, featuring Dr Shruthi Viswanath, Associate Professor at the National Centre for Biological Sciences (NCBS), Tata Institute of Fundamental Research (TIFR), India. Title: Recent Developments in Integrative Structural Modeling of Macromolecular Assemblies Date: Thursday, 27 August Time: 14:00–15:00 BST (UK) Registration: https://events.teams.microsoft.com/event/85e4d258-00dc-4136-a04b-e0358cb54ebf@3f66361c-a87e-4158-8f61-99e82db3cac8 Abstract Integrative structure determination allows us to determine the structures of large macromolecular assemblies by combining data from complementary experimental methods with physical principles, statistical inference, and prior models. It is especially useful for determining structures of assemblies that are recalcitrant to a single experimental method. In the first part, I will talk about our recent efforts in determining the structures of megadalton chromatin remodeling assemblies and cell-cell junctions using Bayesian integrative structural modeling via the Integrative Modeling Platform (IMP, https://integrativemodeling.org<https://integrativemodeling.org/>). I will first describe the application of integrative modeling to characterize the interactome of Histone deacetylase (HDAC). By combining information from X-ray crystallography, homology modeling, AlphaFold2, cross-linking mass spectrometry (XLMS), cryo-electron microscopy, biochemical binding assays, and physical principles, we determined the structures of NuRD, SIN3A, and co-REST HDAC-containing complexes, elucidating the design principles of these co-repressor complexes. As a second example, I will present our recent work on determining the structure of cardiac desmosomes, where integrating AlphaFold3 predictions with cryo-ET, immuno-EM, and biochemical binding data substantially improves the precision and resolution of our previous desmosome structural model. Together, these integrative structures revealed mechanisms by which these complex molecular machines function and assemble; they also enabled us to rationalize mutations from cancers, epithelial, and cardiac diseases. Rapid advances in AI-based structure prediction methods and experiments such as cryo-ET have sparked renewed enthusiasm in integrative modeling. In the second part, I will present our recent work on advancing integrative modeling methods. We found that often, disordered regions (IDRs) of proteins are challenging to localize in integrative structures, since they are usually associated with sparse structural and other interaction data. We developed Disobind, a deep-learning method to predict binding regions for IDRs on a partner, given their sequences. To improve the quality of density maps used in integrative modeling, we are working on PickET, a method for unsupervised particle localization in cryo-electron tomograms. Finally, our lab also develops methods for the PDB-IHM pipeline that are used for validating integrative structures deposited to the PDB.
Speaker Shruthi Viswanath is a computational structural biologist and Associate Professor at NCBS, TIFR, Bangalore. She leads a lab that focuses on determining structures of large macromolecular assemblies using an integrative approach. The lab has recently determined integrative structures of chromatin remodelers and cell-cell junctions; these structures are solved in close collaboration with experimental structural and cell biologists. A significant focus of the lab is on method development for integrative modeling. Some of these methods are part of the Integrative Modeling Platform (IMP, https://integrativemodeling.org<https://integrativemodeling.org/>), and have been adopted by the PDB-IHM pipeline for validating integrative models. See https://isblab.res.in<https://isblab.res.in/> for more details. We hope you will be able to join us for what promises to be an engaging and informative seminar. Best regards, Hima Bindu Kolli On behalf of the DRIIMB<https://driimb.org/> Team ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
