RCSB Protein Data Bank (RCSB.org): delivery of experimentally-determined PDB structures alongside one million computed structure models of proteins from artificial intelligence/machine learning

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 51(D1), P. D488 - D508

Published: Nov. 24, 2022

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), founding member of the Worldwide (wwPDB), is US data center open-access PDB archive. As wwPDB-designated Archive Keeper, RCSB also responsible security. Annually, serves >10 000 depositors three-dimensional (3D) biostructures working on all permanently inhabited continents. delivers from its research-focused RCSB.org web portal to many millions consumers based in virtually every United Nations-recognized country, territory, etc. This Database Issue contribution describes upgrades that created a one-stop-shop open access ∼200 experimentally-determined structures biological macromolecules alongside >1 incorporated Computed Structure Models (CSMs) predicted using artificial intelligence/machine learning methods. 'living resource.' Every structure and CSM integrated weekly with related functional annotations external biodata resources, providing up-to-date information entire corpus 3D biostructure freely available no usage limitations. Within RCSB.org, CSMs are clearly identified as their provenance reliability. Both fully searchable, can be analyzed visualized full complement capabilities.

Language: Английский

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Protein Data Bank: A Comprehensive Review of 3D Structure Holdings and Worldwide Utilization by Researchers, Educators, and Students

Biomolecules, Journal Year: 2022, Volume and Issue: 12(10), P. 1425 - 1425

Published: Oct. 4, 2022

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), funded by the United States National Science Foundation, Institutes of Health, and Department Energy, supports structural biologists (PDB) data users around world. RCSB PDB, a founding member Worldwide (wwPDB) partnership, serves as US center global PDB archive housing experimentally-determined three-dimensional (3D) structure biological macromolecules. As wwPDB-designated Archive Keeper, is also responsible security weekly update archive. tens thousands depositors (using macromolecular crystallography, nuclear magnetic resonance spectroscopy, electron microscopy, micro-electron diffraction) annually working on all permanently inhabited continents. makes available from its research-focused web portal at no charge without usage restrictions to many millions consumers globe. It provides educators, students, general public with an introduction related training materials through outreach education-focused portal. This review article describes growth examines evolution experimental methods determination viewed lens archive, detailed accounting archival holdings their utilization researchers, students worldwide.

Language: Английский

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AlphaFold 2 and NMR Spectroscopy: Partners to Understand Protein Structure, Dynamics and Function

Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 9

Published: May 17, 2022

The artificial intelligence program AlphaFold 2 is revolutionizing the field of protein structure determination as it accurately predicts 3D two thirds human proteome. Its predictions can be used directly structural models or indirectly aids for experimental using X-ray crystallography, CryoEM NMR spectroscopy. Nevertheless, neither afford insight into how proteins fold, nor determine stability dynamics. Rare folds minor alternative conformations are also not predicted by and does forecast impact post translational modifications, mutations ligand binding. remaining third proteome which poorly largely corresponds to intrinsically disordered regions proteins. Key regulation signaling networks, these often form biomolecular condensates amyloids. Fortunately, limitations complemented This approach provides information on folding dynamics well amyloids their modulation conditions, small molecules, mutations, flanking sequence, interactions with other proteins, RNA virus. Together, spectroscopy collaborate advance our comprehension

Language: Английский

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Computational drug development for membrane protein targets

Nature Biotechnology, Journal Year: 2024, Volume and Issue: 42(2), P. 229 - 242

Published: Feb. 1, 2024

Language: Английский

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TMVisDB: Annotation and 3D-visualization of transmembrane proteins

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 168997 - 168997

Published: Feb. 1, 2025

Since the rise of cellular life, transmembrane proteins (TMPs) have been crucial to various processes through their central role as gates and gatekeepers. Despite importance, experimental high-resolution structures for TMPs remain underrepresented due challenges. Given its performance leap, structure predictions begun close gap. However, identifying membrane regions topology in three-dimensional files on a large scale still requires additional silico predictions. Here, we introduce TMVisDB sieve millions predicted TMPs. This resource enables both browsing 46 million visualizing them along with topological annotations without having tap into costly AlphaFold3-style. joins AlphaFoldDB from protein language model (pLM) based method TMbed. We showcase utility analysis two use cases, namely B-lymphocyte antigen CD20 (Homo sapiens) cellulose synthase (Novosphingobium sp. P6W). demonstrate value large-scale analyses findings pertaining all human proteome. is freely available at https://tmvisdb.rostlab.org.

Language: Английский

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Synthesis and Evaluation of a Library of Alternating Amphipathic Copolymers to Solubilize and Study Membrane Proteins

Biomacromolecules, Journal Year: 2022, Volume and Issue: 23(3), P. 743 - 759

Published: Jan. 7, 2022

Amphipathic copolymers such as poly(styrene-maleic acid) (SMA) are promising tools for the facile extraction of membrane proteins (MPs) into native nanodiscs. Here, we designed and synthesized a library well-defined alternating SMA analogues in order to elucidate polymer properties that important MP solubilization stability. efficiency was determined using KcsA from E. coli membranes, general investigated via turbidimetry experiments on membranes coli, yeast mitochondria, synthetic lipids. Remarkably, halogenation dramatically improved all systems, while substituents copolymer backbone resistance Ca2+. Relevant were found include hydrophobic balance, size positioning substituents, rigidity, electronic effects. The thus contributes rational design study MPs.

Language: Английский

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Therapeutic applications of curcumin nanomedicine formulations in cystic fibrosis

Progress in Biomaterials, Journal Year: 2022, Volume and Issue: 11(4), P. 321 - 329

Published: July 29, 2022

Language: Английский

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May the proton motive force be with you: A plant transporter review

Current Opinion in Structural Biology, Journal Year: 2023, Volume and Issue: 79, P. 102535 - 102535

Published: Feb. 14, 2023

As our ecosystems experience challenges associated with climate change, an improved understanding of the fundamental biochemical processes governing plant physiology is needed. Strikingly, current structural information on membrane transporters severely limited compared to other kingdoms life, only 18 unique structures in total. To advance future breakthroughs and insight cell molecular biology, knowledge indispensable. This review summarizes status transporter field. Plants utilize proton motive force (PMF) drive secondary active transport. We discuss PMF, how it relates transport provide a classification PMF driven transport, discussing recently published symporters, antiporters, uniporters from plants.

Language: Английский

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In situ studies of membrane biology by cryo-electron tomography

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 88, P. 102363 - 102363

Published: April 26, 2024

Cryo-electron tomography (cryo-ET) allows high resolution 3D imaging of biological samples in near-native environments. Thus, cryo-ET has become the method choice to analyze unperturbed organization cellular membranes. Here, we briefly discuss current workflows and their application study membrane biology situ, under basal pathological conditions.

Language: Английский

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How the Protein Data Bank changed biology: An introduction to the JBC Reviews thematic series, part 1

Journal of Biological Chemistry, Journal Year: 2021, Volume and Issue: 296, P. 100608 - 100608

Published: Jan. 1, 2021

This collection of articles celebrates the 50th anniversary Protein Data Bank (PDB), single global digital archive biological macromolecular structures. The impact PDB is immense; we have invited a number top researchers in structural biology to illustrate its influence on an array scientific fields. What emerges compelling picture synergism between and explosive progress witnessed many areas. Availability reliable, openly accessible, well-archived information has arguably had more cell molecular than even some enabling technologies such as PCR. We seen science move from time when biologists contributed lion's share structures for discussion within their community any effort achieve in-depth understanding biochemical or question demands interdisciplinary approach built atop underpinnings. A bit history: In 1960s very first protein began be published, groups scientists United States Europe discuss possibility creating these data. Informal formal meetings among interested parties were held, one meeting led petition directed at crystallographic create repository data accessible all. motivation behind discussions many: Those who determining being asked data, which those days was challenging. Others sense that could yield interesting keen able analyze At Cold Spring Harbor Symposium held 1971, group been involved earlier (including us [H.B.]) approached Walter Hamilton, prominent crystallographer Brookhaven National Laboratory (BNL), raised (PDB). He immediately said he would do it promptly flew England initiate collaboration with Olga Kennard, head Cambridge Crystallographic Centre, set up PDB. An announcement fledgling appeared October 1971 (1Protein BankCrystallography: Bank.Nat. New Biol. 1971; 233: 223Crossref PubMed Scopus (69) Google Scholar). Edgar Meyer, also BNL, developed visualization software, Helen Berman work project only handful After Hamilton's untimely death 1973, Tom Koetzle, postdoctoral fellow took over leadership so continued. first, grew slowly, Koetzle put significant convince people deposit Ten years later, members make public deposition mandatory. yet another community—this by Fred Richards Yale—guidelines place International Union Crystallography coordinates condition publication (2International CrystallographyPolicy studies macromolecules.Acta Cryst. 1989; A45: 658Google More deposited, mostly crystallographers. As other methods structure determination emerged, NMR spectroscopy cryo-EM, became part 1999, there 9000 PDB, management taken Research Collaboratory Structural Bioinformatics (RCSB), consortium consisting Rutgers, San Diego Supercomputer Center, Institute Standards Technology. 2003, Worldwide created ensure deposited processed uniform standards (3Berman H.M. Henrick K. Nakamura H. Announcing worldwide Struct. 2003; 10: 980Crossref (1875) initial RCSB Macromolecular Structure Database (MSD) later called (PDBe), Japan (PDBj). 2006, database spectra BioMagResBank (BMRB) joined. last 20 massive growth both terms complexity. Today, contains 175,000 ranging weight less 20,000 Da 380,000 Da. Complexes 1000 components are now emphasis quality control grown, expert task forces making recommendations how best validate determined X-ray crystallography, spectroscopy, 3D electron microscopy. integrative models computed generated several different methods, special underway necessary infrastructure These structures, standards, projects brought life this JBC Reviews. particularly delighted present you, center stage history two key reasons: First, journals require authors reported accepted (4The EditorsInstructions authors.J. Chem. 264: 663-673Abstract Full Text PDF requirement widespread, if not ubiquitous journals. Second, published journal. diverse almost every respect cover multiple areas biochemistry. compendium, tried least spectrum give much learned compare study Many chosen describe field technology evolved attitudes about sharing. paragraphs below, offer previews review included 1 collection. Part 2 will include reviews celebrate additional profoundly touched creation agree most influential ribosome, complex factory made large subunits, each chains RNA molecules, produces proteins through coordinated reactions translation. Peter Moore (Yale University) provides his article historical account ribosome four groups, three whose leaders won Nobel Prizes 2009 (5Moore P.B. ribosome.J. 2021; 296: 100561Abstract (3) points out challenges presented retrospect, clear fortunate early curators Nucleic Acid project, them apply experience insight into representing game-changing Moore's captures transition reliance crystallography machines current practice using microscopy why method choice assemblies. addition description impactful adds unique reflections participation "birth" enables him offer. comments "state play" amazing Meeting described above. It surprising after reading remarks outcome meeting. importance details virus highlighted during pandemic. review, John 'Jack' Johnson Art Olson (The Scripps Institute) focus icosahedral viruses, starting plant viruses 1980s followed human rhinovirus (6Johnson J.E. A.J. Icosahedral Bank.J. 100554Abstract (8) Now hundreds They point that, although intense interest community, difficult communicate virologists. graphics program, VIPER, provided pathway basis way represents increasing use crystallographers Johnson's publications (7Johnson Confessions crystallographer.Microscopy. 2013; 62: 69-79Crossref (6) shares experiences co-opting computer programs movies discovery DNA fiber diffraction seminal event paved biology. Yet, decades before atomic level defined sequence Richard Dickerson's laboratory California Stephen Neidle (University College London School Pharmacy) describes earliest sequence-dependent diversity oligonucleotides recognition (8Neidle S. Beyond double helix: PDB.J. 100553Abstract (9) ability G-rich tracts form quadruplexes, far biophysical artifact, underlies role telomeres allows assume variety functional topologies. And, recently, deoxyribozymes cleave discovered analyzed. highlights important plays ensuring used computational analyses drug design. 50 evolution structure. Eric Westhof Strasbourg) late Neocles Leontis (Bowling Green trace history, determinations tRNA small fragments helix (9Westhof E. N.B. RNA-centric narrative around 100555Abstract (5) ribozymes opened door world, continues surprise new folds functions. rich folding rules derived discussed, modeling efforts based rules. value assembling curating validation. comment played testbed formats allow assemblies properly archived includes tribute Leontis, scholar longtime collaborator. regulatory processes rely surface composition proteins—the "face" they world them. eukaryotic systems, carbohydrate modifications surfaces extremely widespread. decorations glycoproteins proved elusive structurally years, because heavy bacterial expression systems preparation adequate amounts crystallography. addition, heterogeneity dynamic character stymied years. James Prestegard Georgia) breakthroughs descriptions resulting insights elucidated puzzles (10Prestegard J.H. perspective PDB's glycobiology.J. 100556Abstract Central challenging area deployment determine compositions glycoproteins. welcomed represented example where synergistic essential advances. Membrane intimate dependence integrity anisotropic environment function. Robert Stroud California, Francisco) coworkers beautifully occurred membrane proteins, achieved productive crystallization growing examples leading stunning advances our (11Li F. Egea P.F. Vecchio Asial I. Gupta M. Paulino J. Bajaj R. Dickinson M.S. Ferguson-Miller Monk B.C. R.M. Highlighting function: celebration 100557Abstract (23) greatly facilitated recent cryo-EM. Indeed, cryo-EM emerged fastest determination. Wah Chiu (Stanford colleagues provide overview technical sample preparation, instrumentation, software remarkable vast improvements resolution (12Chiu W. Schmid M.F. Pintilie G.D. Lawson C.L. Evolution standardization dissemination jointly EMDB.J. 100560Abstract (7) discusses activities archives maps models, possible types via system. development validation criteria "Challenges" organized Electron Microscopy Resource (https://challenges.emdataresource.org/). end piece highlighting reports raising final Computational major leaps lifetime no measure available solved Tanja Kortemme her colleague Xingjie Pan design enabled access extensive (13Pan X. T. Recent de novo design: Principles, applications.J. 100558Abstract (37) principles Nature illustrates evolutionarily honed build guiding designed crucial. Review, seeing landmark goals: novel desired functions, never previously observed, mimicking naturally occurring families proteins. Not open doors engineering but inform prediction, strikingly illustrated artificial intelligence prediction (14Senior A.W. Evans Jumper Kirkpatrick Sifre L. Qin C. Žídek A. Nelson A.W.R. Bridgland Penedones Petersen Simonyan Crossan Kohli P. et al.Improved potentials deep learning.Nature. 2020; 577: 706-710Crossref (1173) fed impressive developments exploit breadth Barry Honig (Columbia area, biology, tackle relationships (15Murray D. Petrey B. Integrating biology.J. 100562Abstract can lead structure-informed turn reveal interactomes testable genetic screens. long run, may therapeutic strategies linking space chemical compound space. Knowledge health disease discovery. Burley (Rutgers stages development: target validation, druggability, small-molecule binding targets, structure-guided optimization, optimization pharmacokinetic properties (16Burley S.K. Impact development.J. 100559Abstract (11) quantitative approval process, case approaches approvals antineoplastic drugs illustration. splendid scholarly forward-looking Reviews testament power depositories, discoveries fueled serving premier example. hope you join saluting prescience establishing half century ago basking beauty fundamental knowledge There come celebratory collection: stay tuned 2! declare conflicts contents article. supported NIH Grant R35 GM118161 G. content solely responsibility does necessarily represent official views Institutes Health.

Language: Английский

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