Crystallography - Molecular architecture • Symmetry (molecule, stacking objects) point groups, plane groups, space groups • Crystal structure determination using X-ray diffraction • Cambridge Structural Database What is: crystallography – crystal ? • Krústallos (Gr Frozen water) • solid state of matter • regular external faces geometrical law - Steno (1669) angle between two corresponding faces is constant • regular internal structure Keppler (New year’s day 1611) • Hauy (1784): identical building blocks What is: crystallography – crystal ? • originaly part of geology - mineralogy • discovery X-rays (Rưntgen, 1895, NP 1901) • diffraction experiment crystal (von Laue, 1912, NP 1914) • structure determination simple salts (Bragg, 1913, NP 1915) • since then more and more complex structures Crystallography evoluates from description of external structure to internal structure! Relation to other sciences… Structure and properties of… • minerals • metals, alloys • (in)organic compounds • polymers • biomolecules mineralogy material science chemistry, pharmacy solid-state physics polymer science biochemistry, molecular biology, medecine With the help of… mathematics informatics Relation to other sciences… Some examples… CHEMISTRY C60, fullerene Proven by X-ray (derivative) Relation to other sciences… Some examples… BIOCHEMISTRY NP Chemistry 2003 – structure determination water- ion channels Relation to other sciences… Some examples… PHARMACY Relation to other sciences… Some examples… POLYMER SCIENCES Polyethylene Importance crystallinity Importance symmetry External order of a crystal reflects an internal submicroscopic order Symmetry is important in almost all disciplines of science, art and society Some important realisations crystallography • theory electrostatic bond in inorganic ion structures • proof tetrahedral carbon atom • structure elucidation benzene ring • proof existence H-bond • -helix, -plate in proteins • DNA-model • determination absolute configuration Interpretation of electron density density maps Chapter Interpretation of electron maps Calculate electron density map (= Fourier synthesis) – contour – grid Tracing of CA backbone + positioning of side chains Tracing of CA backbone + positioning of side chains For tryptophan side chain… Resolution (Å) of a crystal structure determination (minimum d-value corresponding to maximum 2-value) 1Å Atoms 3Å Residues, side chains 4Å Sec structure, molecules From 0.5 to 6.0 Å resolution… Chapter 10 Refinement techniques • iterative process of improving agreement between Fo and Fc  =  whkl (|Fo|-|Fc|)2hkl • possible parameters for least-squares adjustment: - atomic positions (3) - occupancies (1) - temperature factors (1 or 6) • follow the refinement by monitoring the R-value of residual value: • Locate water molecules, ions … from difference Fourier synthesis (xyz) = 1/V h k l (Fo-Fc)hkl exp -2i(hx+ky+lz) Criteria: peak height, distances, H-bonds, co-ordination, … Fo-Fc map • is difference map Δ(xyz) = 1/V    (Fo-Fc)hkl exp -2i(hx+ky+lz) h k l • judging the model using structural parameters - R-value (check also resolution and sigma cut-off) - rms deviations for bond lengths (< 0.02Å) and angles (< 4°) from ideal values - standard deviations ? - difference Fourier - resolution - thermal parameters • deposition coordinates and structure factors (PDB, NDB, CSD, …) • Crystallographic Information File (CIF and mmCIF) loop_ _atom_site.group_PDB _atom_site.type_symbol _atom_site.label_atom_id _atom_site.label_comp_id _atom_site.label_asym_id _atom_site.label_seq_id _atom_site.label_alt_id _atom_site.Cartn_x _atom_site.Cartn_y _atom_site.Cartn_z _atom_site.occupancy _atom_site.B_iso_or_equiv _atom_site.footnote_id _atom_site.auth_seq_id _atom_site.id ATOM N N VAL A 11 25.369 30.691 11.795 1.00 17.93 11 ATOM C CA VAL A 11 25.970 31.965 12.332 1.00 17.75 11 ATOM C C VAL A 11 25.569 32.010 13.808 1.00 17.83 11 ATOM O O VAL A 11 24.735 31.190 14.167 1.00 17.53 11 ATOM C CB VAL A 11 25.379 33.146 11.540 1.00 17.66 11 ATOM C CG1 VAL A 11 25.584 33.034 10.030 1.00 18.86 11 ATOM C CG2 VAL A 11 23.933 33.309 11.872 1.00 17.12 11 ATOM N N THR A 12 26.095 32.930 14.590 1.00 18.97 12 ATOM C CA THR A 12 25.734 32.995 16.032 1.00 19.80 12 ATOM C C THR A 12 24.695 34.106 16.113 1.00 20.92 12 10 ATOM O O THR A 12 24.869 35.118 15.421 1.00 21.84 12 11 … Cambridge Crystallographic Data Centre CCDC • established in 1965 • first numerical scientific database • now non-profit organisation (1989) • distributes CSD System to more than 850 universities and 120 companies • related software and research  new building since 1992 The Cambridge Structural Database (CSD) • carbon-containing molecules : organics, organometallics, metal complexes • peptides up to 24 residues (rest in PDB) • mono-, di- and trinucleotides (rest in NDB) • x-ray and neutron diffraction Also : ICSD and CRYSTMET ! Cambridge Structural Database Worldwide repository of validated small-molecule crystal structures Lamotrigine Acta Cryst., Sect.C:Cryst Struct Commun (2009), 65, o460 Refcode: EFEMUX01 CSD Growth 1970-2010 Dec 09 – 500,000th structure milestone reached Release 2013 – 631,626 structures Database plus Access Software Acta Cryst., B58, 380-388 & 389-397, 2002 *free downloads http://www.ccdc.cam.ac.uk/ Organisation of the CSD Searching the CSD - ConQuest CSD-5 O Demonstration Olex2 1688 reflections measured Space group P212121 Start with S position CH3 S CH3 O