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New paper 2/2: GPCRmd uncovers the dynamics of the 3D-GPCRome

Pi, 24.07.2020 - 18:26
The second paper is Rodríguez-Espigares, I., Torrens-Fontanals, M., Tiemann, J.K.S. et al. GPCRmd uncovers the dynamics of the 3D-GPCRome. Nat Methods (2020). 10.1038/s41592-020-0884-y here, your computations have been used to build a database of configurations for most types and subtypes of GPCR-class proteins. GPCRs are "do-all" receptors - there are many many subtypes, each with activators and inhibitors. The GPCRmd database provides for the first time a *systematic* coverage of their dynamics. G-protein-coupled receptors (GPCRs) are involved in numerous physiological processes and are the most frequent targets of approved drugs. The explosion in the number of new three-dimensional (3D) molecular structures of GPCRs (3D-GPCRome) over the last decade has greatly advanced the mechanistic understanding and drug design opportunities for this protein family. Molecular dynamics (MD) simulations have become a widely established technique for exploring the conformational landscape of proteins at an atomic level. However, the analysis and visualization of MD simulations require efficient storage resources and specialized software. Here we present GPCRmd (http://gpcrmd.org/), an online platform that incorporates web-based visualization capabilities as well as a comprehensive and user-friendly analysis toolbox that allows scientists from different disciplines to visualize, analyze and share GPCR MD data. GPCRmd originates from a community-driven effort to create an open, interactive and standardized database of GPCR MD simulations. ... 14310 1 107681600 101936 2 96720000 483287 3 83904600 500240 4 74393800 306281 5 57790200 93201 6 55775200 100499 7 53115400 504924 8 51664600 25378 9 50858600 62100 10 32240000 125700 11 31837000 73475 12 29983200 69336 13 27645800 28899 14 23615800 31053 15 22406800 146761 16 21439600 497873 17 20230600 13127 18 20069400 36684 19 19666400 126468 20 19021600
Kategórie: Novinky z projektov

New paper 1/2: PlayMolecule CrypticScout: Predicting Protein Cryptic Sites Using Mixed-Solvent Molecular Simulation

Pi, 24.07.2020 - 18:23
Two recent papers which came out with results from GPUGRID. First, PlayMolecule CrypticScout: Predicting Protein Cryptic Sites Using Mixed-Solvent Molecular Simulations Gerard Martinez-Rosell, Silvia Lovera, Zara A. Sands, and Gianni De Fabritiis Journal of Chemical Information and Modeling 2020 60 (4), 2314-2324 DOI: 10.1021/acs.jcim.9b01209 In this paper (and the corresponding live system) GPUGRID's computations are used to power a search for elusive (transient) pockets which may become drug targets. Thanks for the contributions! Cryptic pockets are protein cavities that remain hidden in resolved apo structures and generally require the presence of a co-crystallized ligand to become visible. Finding new cryptic pockets is crucial for structure-based drug discovery to identify new ways of modulating protein activity and thus expand the druggable space. We present here a new method and associated web application leveraging mixed-solvent molecular dynamics (MD) simulations using benzene as a hydrophobic probe to detect cryptic pockets. Our all-atom MD-based workflow was systematically tested on 18 different systems and 5 additional kinases and represents the largest validation study of this kind. CrypticScout identifies benzene probe binding hotspots on a protein surface by mapping probe occupancy, residence time, and the benzene occupancy reweighed by the residence time. The method is presented to the scientific community in a web application available via www.playmolecule.org using a distributed computing infrastructure to perform the simulations. List of most-contributing users: User Rank Credits 101936 1 4639746 14310 2 4450949 483287 3 3535477 103037 4 2362054 500240 5 1986559 25378 6 1969784 504924 7 1945416 100499 8 1834758 73475 9 1796967 125700 10 1755579 126468 11 1651313 306281 12 1638950 62100 13 1542475 21233 14 1536750 535400 15 1364758 13127 16 1161000 509733 17 1035000 28899 18 973950 543022 19 971404 89682 20 946350
Kategórie: Novinky z projektov