5px3 Citations

A multi-crystal method for extracting obscured crystallographic states from conventionally uninterpretable electron density.

OpenAccess logo Nat Commun 8 15123 (2017)
Related entries: 5pb7, 5pb8, 5pb9, 5pba, 5pbb, 5pbc, 5pbd, 5pbe, 5pbf, 5pbg, 5pbh, 5pbi, 5pbj, 5pbk, 5pbl, 5pbm, 5pbn, 5pbo, 5pbp, 5pbq, 5pbr, 5pbs, 5pbt, 5pbu, 5pbv, 5pbw, 5pbx, 5pby, 5pbz, 5pc0, 5pc1, 5pc2, 5pc3, 5pc4, 5pc5, 5pc6, 5pc7, 5pc8, 5pc9, 5pca, 5pcb, 5pcc, 5pcd, 5pce, 5pcf, 5pcg, 5pch, 5pci, 5pcj, 5pck, 5pcl, 5pcm, 5pcn, 5pco, 5pcp, 5pcq, 5pcr, 5pcs, 5pct, 5pcu, 5pcv, 5pcw, 5pcx, 5pcz, 5pd0, 5pd1, 5pd2, 5pd3, 5pd4, 5pd5, 5pd6, 5pd7, 5pd8, 5pd9, 5pda, 5pdb, 5pdc, 5pdd, 5pde, 5pdf, 5pdg, 5pdh, 5pdi, 5pdj, 5pdk, 5pdl, 5pdm, 5pdn, 5pdo, 5pdp, 5pdq, 5pdr, 5pds, 5pdt, 5pdu, 5pdv, 5pdw, 5pdx, 5pdy, 5pdz, 5pe0, 5pe1, 5pe2, 5pe3, 5pe4, 5pe5, 5pe6, 5pe7, 5pe8, 5pe9, 5pea, 5peb, 5pec, 5ped, 5pee, 5pef, 5peg, 5peh, 5pei, 5pej, 5pek, 5pel, 5pem, 5pen, 5peo, 5peq, 5per, 5pes, 5pet, 5peu, 5pev, 5pew, 5pex, 5pey, 5pez, 5pf0, 5pf1, 5pf2, 5pf3, 5pf4, 5pf5, 5pf6, 5pf7, 5pf8, 5pf9, 5pfa, 5pfb, 5pfc, 5pfd, 5pfe, 5pff, 5pfg, 5pfh, 5pfi, 5pfj, 5pfl, 5pfm, 5pfn, 5pfo, 5pfp, 5pfq, 5pfr, 5pfs, 5pft, 5pfu, 5pfv, 5pfw, 5pfx, 5pfy, 5pfz, 5pg0, 5pg1, 5pg2, 5pg3, 5pg4, 5pg5, 5pg6, 5pg7, 5pg8, 5pg9, 5pga, 5pgb, 5pgc, 5pgd, 5pge, 5pgf, 5pgg, 5pgh, 5pgi, 5pgj, 5pgk, 5pgl, 5pgn, 5pgo, 5pgp, 5pgq, 5pgr, 5pgs, 5pgt, 5ph0, 5ph1, 5ph2, 5ph3, 5ph4, 5ph5, 5ph6, 5ph7, 5ph8, 5ph9, 5pha, 5phb, 5phc, 5phd, 5phe, 5phf, 5phg, 5phh, 5phi, 5phj, 5phk, 5phl, 5phm, 5phn, 5pho, 5php, 5phq, 5phr, 5phs, 5pht, 5phu, 5phv, 5phw, 5phx, 5phy, 5phz, 5pi0, 5pi1, 5pi2, 5pi3, 5pi4, 5pi5, 5pi6, 5pi7, 5pi8, 5pi9, 5pia, 5pib, 5pic, 5pid, 5pie, 5pif, 5pig, 5pih, 5pii, 5pij, 5pik, 5pil, 5pim, 5pin, 5pio, 5pip, 5piq, 5pir, 5pis, 5pit, 5piu, 5piv, 5piw, 5pix, 5piy, 5piz, 5pj0, 5pj1, 5pj2, 5pj3, 5pj4, 5pj5, 5pj6, 5pj7, 5pj8, 5pj9, 5pja, 5pjb, 5pjc, 5pjd, 5pje, 5pjf, 5pjg, 5pjh, 5pji, 5pjj, 5pjk, 5pjl, 5pjm, 5pjn, 5pjo, 5pjp, 5pjq, 5pjr, 5pjs, 5pjt, 5pju, 5pjv, 5pjw, 5pjx, 5pjy, 5pjz, 5pk0, 5pk1, 5pk2, 5pk3, 5pk4, 5pk5, 5pk6, 5pk7, 5pk8, 5pk9, 5pka, 5pkb, 5pkc, 5pkd, 5pke, 5pkf, 5pkg, 5pkh, 5pki, 5pkj, 5pkk, 5pkl, 5pkm, 5pkn, 5pko, 5pkp, 5pkq, 5pkr, 5pks, 5pkt, 5pku, 5pkv, 5pkw, 5pkx, 5pky, 5pkz, 5pl0, 5pl1, 5pl2, 5pl3, 5pl4, 5pl5, 5pl6, 5pl7, 5pl8, 5pl9, 5pla, 5plb, 5plc, 5pld, 5ple, 5plf, 5plg, 5plh, 5pli, 5plj, 5plk, 5pll, 5plm, 5pln, 5plo, 5plp, 5plq, 5plr, 5pls, 5plt, 5plu, 5plv, 5plw, 5plx, 5ply, 5plz, 5pm0, 5pm1, 5pm2, 5pm3, 5pm4, 5pm5, 5pm6, 5pm7, 5pm8, 5pm9, 5pma, 5pmb, 5pmc, 5pmd, 5pme, 5pmf, 5pmg, 5pmh, 5pmi, 5pmj, 5pmk, 5pml, 5pmm, 5pmn, 5pmo, 5pmp, 5pmq, 5pmr, 5pms, 5pmt, 5pmu, 5pmv, 5pmw, 5pmx, 5pmy, 5pmz, 5pn0, 5pn1, 5pn2, 5pn3, 5pn4, 5pn5, 5pn6, 5pn7, 5pn8, 5pn9, 5pna, 5pnb, 5pnc, 5pnd, 5pne, 5pnf, 5png, 5pnh, 5pni, 5pnj, 5pnk, 5pnl, 5pnm, 5pnn, 5pno, 5pnp, 5pnq, 5pnr, 5pns, 5pnu, 5pnv, 5pnw, 5pnx, 5pny, 5pnz, 5po0, 5po1, 5po2, 5po3, 5po4, 5po5, 5po6, 5po7, 5po8, 5po9, 5poa, 5pob, 5poc, 5pod, 5poe, 5pof, 5pog, 5poh, 5poi, 5poj, 5pok, 5pol, 5pom, 5pon, 5poo, 5pop, 5poq, 5por, 5pos, 5pot, 5pou, 5pov, 5pow, 5pox, 5poy, 5poz, 5pp0, 5pp1, 5pp2, 5pp3, 5pp4, 5pp5, 5pp6, 5pp7, 5pp8, 5pp9, 5ppa, 5ppb, 5ppc, 5ppd, 5ppe, 5ppf, 5ppg, 5pph, 5ppi, 5ppj, 5ppk, 5ppl, 5ppm, 5ppn, 5ppo, 5ppp, 5ppq, 5ppr, 5pps, 5ppt, 5ppu, 5ppv, 5ppw, 5ppx, 5ppy, 5ppz, 5pq0, 5pq1, 5pq2, 5pq3, 5pq4, 5pq5, 5pq6, 5pq7, 5pq8, 5pq9, 5pqa, 5pqb, 5pqc, 5pqd, 5pqe, 5pqf, 5pqg, 5pqh, 5pqi, 5pqj, 5pqk, 5pql, 5pqm, 5pqn, 5pqo, 5pqp, 5pqq, 5pqr, 5pqs, 5pqt, 5pqu, 5pqv, 5pqw, 5pqx, 5pqy, 5pqz, 5pr0, 5pr1, 5pr2, 5pr4, 5pr5, 5pr6, 5pr7, 5pr8, 5pr9, 5pra, 5prb, 5prd, 5pre, 5prf, 5prg, 5prh, 5pri, 5prj, 5prk, 5prl, 5prm, 5pro, 5prp, 5prq, 5prr, 5prs, 5prt, 5pru, 5prv, 5prw, 5prx, 5pry, 5prz, 5ps0, 5ps1, 5ps2, 5ps3, 5ps4, 5ps5, 5ps6, 5ps7, 5ps8, 5ps9, 5psa, 5psb, 5psc, 5psd, 5pse, 5psf, 5psg, 5psh, 5psi, 5psj, 5psk, 5psl, 5psm, 5psn, 5pso, 5psp, 5psq, 5psr, 5pss, 5pst, 5psu, 5psv, 5psw, 5psx, 5psy, 5psz, 5pt0, 5pt1, 5pt2, 5pt3, 5pt4, 5pt5, 5pt6, 5pt7, 5pt8, 5pt9, 5pta, 5ptb, 5ptc, 5pte, 5ptf, 5ptg, 5pth, 5ptj, 5ptk, 5ptl, 5ptm, 5ptn, 5pto, 5ptq, 5ptr, 5pts, 5ptt, 5ptu, 5ptv, 5ptw, 5ptx, 5pty, 5ptz, 5pu0, 5pu1, 5pu2, 5pu3, 5pu4, 5pu5, 5pu6, 5pu7, 5pu8, 5pu9, 5pua, 5pub, 5puc, 5pud, 5pue, 5puf, 5pug, 5puh, 5pui, 5puj, 5puk, 5pul, 5pum, 5pun, 5puo, 5pup, 5puq, 5pur, 5pus, 5put, 5puu, 5puv, 5puw, 5pux, 5puy, 5puz, 5pv0, 5pv1, 5pv2, 5pv3, 5pv4, 5pv5, 5pv6, 5pv7, 5pv8, 5pv9, 5pva, 5pvb, 5pvc, 5pvd, 5pve, 5pvf, 5pvg, 5pvh, 5pvi, 5pvj, 5pvk, 5pvl, 5pvm, 5pvn, 5pvo, 5pvp, 5pvq, 5pvr, 5pvs, 5pvt, 5pvu, 5pvv, 5pvw, 5pvx, 5pvy, 5pvz, 5pw0, 5pw1, 5pw2, 5pw3, 5pw4, 5pw5, 5pw6, 5pw7, 5pw8, 5pw9, 5pwa, 5pwb, 5pwc, 5pwd, 5pwe, 5pwf, 5pwg, 5pwh, 5pwi, 5pwj, 5pwk, 5pwl, 5pwm, 5pwn, 5pwo, 5pwp, 5pwq, 5pwr, 5pws, 5pwt, 5pwu, 5pwv, 5pww, 5pwx, 5pwy, 5pwz, 5px0, 5px1, 5px2, 5px4, 5px5, 5px6, 5px7, 5px8, 5px9, 5pxa, 5pxb, 5pxc, 5pxd, 5pxe, 5pxf, 5pxg, 5pxh, 5pxi, 5pxj, 5pxk, 5pxl, 5pxm, 5pxn, 5pxo, 5pxp, 5pxq, 5pxr, 5pxs, 5pxt, 5pxu, 5pxv, 5pxw, 5pxx, 5pxy, 5pxz, 5py0, 5py1, 5py2, 5py3, 5py4, 5py5, 5py6, 5py7, 5py8, 5py9, 5pya, 5pyb, 5pyc, 5pyd, 5pye, 5pyf, 5pyg, 5pyh, 5pyi, 5pyj, 5pyk, 5pyl, 5pym, 5pyn, 5pyo, 5pyp, 5pyq, 5pyr, 5pys, 5pyt, 5pyu, 5pyv, 5pyw, 5pyx, 5pyy, 5pyz, 5pz0, 5pz1, 5pz2, 5pz3, 5pz4, 5pz5, 5pz6, 5pz7, 5pz8, 5pz9, 5pza, 5pzb, 5pzc, 5pzd, 5pze, 5pzf, 5pzg, 5pzh, 5pzi, 5pzj

Cited: 104 times
EuropePMC logo PMID: 28436492

Abstract

In macromolecular crystallography, the rigorous detection of changed states (for example, ligand binding) is difficult unless signal is strong. Ambiguous ('weak' or 'noisy') density is experimentally common, since molecular states are generally only fractionally present in the crystal. Existing methodologies focus on generating maximally accurate maps whereby minor states become discernible; in practice, such map interpretation is disappointingly subjective, time-consuming and methodologically unsound. Here we report the PanDDA method, which automatically reveals clear electron density for the changed state-even from inaccurate maps-by subtracting a proportion of the confounding 'ground state'; changed states are objectively identified from statistical analysis of density distributions. The method is completely general, implying new best practice for all changed-state studies, including the routine collection of multiple ground-state crystals. More generally, these results demonstrate: the incompleteness of atomic models; that single data sets contain insufficient information to model them fully; and that accuracy requires further map-deconvolution approaches.

Reviews citing this publication (16)

  1. WD40 repeat domain proteins: a novel target class? Schapira M, Tyers M, Torrent M, Arrowsmith CH. Nat Rev Drug Discov 16 773-786 (2017)
  2. Current perspectives in fragment-based lead discovery (FBLD). Lamoree B, Hubbard RE. Essays Biochem 61 453-464 (2017)
  3. Protein X-ray Crystallography and Drug Discovery. Maveyraud L, Mourey L. Molecules 25 E1030 (2020)
  4. Concepts and Core Principles of Fragment-Based Drug Design. Kirsch P, Hartman AM, Hirsch AKH, Empting M. Molecules 24 E4309 (2019)
  5. Where is crystallography going? Grimes JM, Hall DR, Ashton AW, Evans G, Owen RL, Wagner A, McAuley KE, von Delft F, Orville AM, Sorensen T, Walsh MA, Ginn HM, Stuart DI. Acta Crystallogr D Struct Biol 74 152-166 (2018)
  6. A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process. Noske GD, Nakamura AM, Gawriljuk VO, Fernandes RS, Lima GMA, Rosa HVD, Pereira HD, Zeri ACM, Nascimento AFZ, Freire MCLC, Fearon D, Douangamath A, von Delft F, Oliva G, Godoy AS. J Mol Biol 433 167118 (2021)
  7. Role of Computational Methods in Going beyond X-ray Crystallography to Explore Protein Structure and Dynamics. Srivastava A, Nagai T, Srivastava A, Miyashita O, Tama F. Int J Mol Sci 19 E3401 (2018)
  8. Structural Biology and the Design of New Therapeutics: From HIV and Cancer to Mycobacterial Infections: A Paper Dedicated to John Kendrew. Thomas SE, Mendes V, Kim SY, Malhotra S, Ochoa-Montaño B, Blaszczyk M, Blundell TL. J Mol Biol 429 2677-2693 (2017)
  9. Best practices for time-resolved serial synchrotron crystallography. Schulz EC, Yorke BA, Pearson AR, Mehrabi P. Acta Crystallogr D Struct Biol 78 14-29 (2022)
  10. New developments in crystallography: exploring its technology, methods and scope in the molecular biosciences. Helliwell JR. Biosci Rep 37 BSR20170204 (2017)
  11. Repurposing an Antiviral Drug against SARS-CoV-2 Main Protease. Sarkar A, Mandal K. Angew Chem Int Ed Engl 60 23492-23494 (2021)
  12. Advances in methods for atomic resolution macromolecular structure determination. Thompson MC, Yeates TO, Rodriguez JA. F1000Res 9 F1000 Faculty Rev-667 (2020)
  13. The SGC beyond structural genomics: redefining the role of 3D structures by coupling genomic stratification with fragment-based discovery. Bradley AR, Echalier A, Fairhead M, Strain-Damerell C, Brennan P, Bullock AN, Burgess-Brown NA, Carpenter EP, Gileadi O, Marsden BD, Lee WH, Yue W, Bountra C, von Delft F. Essays Biochem 61 495-503 (2017)
  14. Using Structure-guided Fragment-Based Drug Discovery to Target Pseudomonas aeruginosa Infections in Cystic Fibrosis. Arif SM, Floto RA, Blundell TL. Front Mol Biosci 9 857000 (2022)
  15. Medicinal chemistry strategies towards the development of non-covalent SARS-CoV-2 Mpro inhibitors. Song L, Gao S, Ye B, Yang M, Cheng Y, Kang D, Yi F, Sun JP, Menéndez-Arias L, Neyts J, Liu X, Zhan P. Acta Pharm Sin B 14 87-109 (2024)
  16. SARS-CoV-2 proteins structural studies using synchrotron radiation. Kosenko M, Onkhonova G, Susloparov I, Ryzhikov A. Biophys Rev 15 1185-1194 (2023)

Articles citing this publication (88)