High‐resolution crystallography and drug design

Ultra‐high‐resolution X‐ray crystallography of macromolecules (i.e. resolution better than 0.8 Å) is a rising field that promises to provide new insight into the structure–function relationships of biomacromolecules. The picture emerging from macromolecular structures at this resolution is far more complex than previously understood, requiring for its study improved tools for structure refinement, analysis and annotation. Some of these problems were highlighted during the recent High Resolution Drug Design Meeting (Bischenberg‐Strasbourg, France, 13–16 May 2004). We will review here some of the results and discussions that took place during that meeting and elaborate on the trends and challenges ahead in this emerging new field of research. Copyright © 2005 John Wiley & Sons, Ltd.

[1]  Spencer J. Williams,et al.  Atomic resolution analyses of the binding of xylobiose-derived deoxynojirimycin and isofagomine to xylanase Xyn10A. , 2004, Chemical communications.

[2]  M. DePristo,et al.  Heterogeneity and inaccuracy in protein structures solved by X-ray crystallography. , 2004, Structure.

[3]  Mike Bray,et al.  Cyanovirin-N binds to the viral surface glycoprotein, GP1,2 and inhibits infectivity of Ebola virus. , 2003, Antiviral research.

[4]  C. Lecomte,et al.  Ultra-high-resolution X-ray structure of proteins , 2004, Cellular and Molecular Life Sciences CMLS.

[5]  D. Jayatilaka,et al.  Wavefunctions derived from experiment. I. Motivation and theory. , 2001, Acta crystallographica. Section A, Foundations of crystallography.

[6]  J. Ladbury,et al.  Survey of the year 2005: literature on applications of isothermal titration calorimetry , 2007, Journal of molecular recognition : JMR.

[7]  Gerhard Klebe,et al.  Crystallographic study of inhibitors of tRNA-guanine transglycosylase suggests a new structure-based pharmacophore for virtual screening. , 2004, Journal of molecular biology.

[8]  Gerhard Klebe,et al.  Relibase: design and development of a database for comprehensive analysis of protein-ligand interactions. , 2003, Journal of molecular biology.

[9]  Irene T Weber,et al.  High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains. , 2004, Journal of molecular biology.

[10]  Victor S Lamzin,et al.  Breaking good resolutions with ARP/wARP. , 2004, Journal of synchrotron radiation.

[11]  V Lamzin,et al.  Accurate protein crystallography at ultra-high resolution: valence electron distribution in crambin. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Jan Hermans,et al.  Promise of advances in simulation methods for protein crystallography: implicit solvent models, time-averaging refinement, and quantum mechanical modeling. , 2003, Methods in enzymology.

[13]  Raul E Cachau,et al.  Structural information content at high resolution: MAD versus native. , 2003, Methods in enzymology.

[14]  Chernov Aa,et al.  View on biocrystallization from Jena, 2002 , 2002 .

[15]  R Giegé,et al.  From conventional crystallization to better crystals from space: a review on pilot crystallogenesis studies with aspartyl-tRNA synthetases. , 2002, Acta crystallographica. Section D, Biological crystallography.

[16]  P. Kuhn,et al.  The 0.78 A structure of a serine protease: Bacillus lentus subtilisin. , 1998, Biochemistry.

[17]  Patrick C. Mowery,et al.  Semiempirical SCF MO calculations on electrophilic aromatic substitution , 1970 .

[18]  Richard Giegé,et al.  Investigating the nucleation of protein crystals with hydrostatic pressure , 2003 .

[19]  Karen Heyman Better structures through synergy , 2004 .

[20]  Leo Radom,et al.  Molecular orbital theory of the electronic structure of organic compounds. XII. Conformations, stabilities, and charge distributions in monosubstituted benzenes , 1972 .

[21]  Richard Giegé,et al.  Pressure versus pH phase diagrams of two lysozymes crystallized in agarose gel , 2003 .

[22]  G. Klebe,et al.  Strategies for the design of inhibitors of aldose reductase, an enzyme showing pronounced induced-fit adaptations , 2004, Cellular and Molecular Life Sciences CMLS.

[23]  Dino Moras,et al.  Identification of an alternative ligand-binding pocket in the nuclear vitamin D receptor and its functional importance in 1alpha,25(OH)2-vitamin D3 signaling. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Claude Lecomte,et al.  A comparison between experimental and theoretical aspherical-atom scattering factors for charge-density refinement of large molecules. , 2004, Acta crystallographica. Section A, Foundations of crystallography.

[25]  Raul E. Cachau,et al.  DYNGA: a general purpose QM-MM-MD program. I. Application to water , 2003 .

[26]  Eric Westhof,et al.  RNA as a Drug Target: The Case of Aminoglycosides , 2003, Chembiochem : a European journal of chemical biology.

[27]  Richard J Morris,et al.  ARP/wARP and automatic interpretation of protein electron density maps. , 2003, Methods in enzymology.

[28]  Connie Darmanin,et al.  Probing the ultra-high resolution structure of aldose reductase with molecular modelling and noncovalent mass spectrometry. , 2004, Bioorganic & medicinal chemistry.

[29]  Kurt Wüthrich,et al.  Nmr in drug discovery , 2002, Nature Reviews Drug Discovery.

[30]  R E Cachau,et al.  Ultrahigh resolution drug design I: Details of interactions in human aldose reductase–inhibitor complex at 0.66 Å , 2004, Proteins.

[31]  G Bricogne,et al.  Phasing in the presence of severe site-specific radiation damage through dose-dependent modelling of heavy atoms. , 2004, Acta crystallographica. Section D, Biological crystallography.

[32]  Wolfgang Jahnke,et al.  Second-site NMR screening and linker design. , 2003, Current topics in medicinal chemistry.

[33]  G. Tsoucaris,et al.  Ab initio determination of a crystal structure by means of the Schrödinger equation. , 2002, Acta crystallographica. Section A, Foundations of crystallography.

[34]  P Gros,et al.  Inclusion of thermal motion in crystallographic structures by restrained molecular dynamics. , 1990, Science.

[35]  I. Brown,et al.  The Chemical Bond in Inorganic Chemistry: The Bond Valence Model , 2002 .

[36]  Stuart Blackman The right research mix , 2004 .

[37]  K. Fukui,et al.  Role of frontier orbitals in chemical reactions. , 1982, Science.

[38]  George M Sheldrick,et al.  Substructure solution with SHELXD. , 2002, Acta crystallographica. Section D, Biological crystallography.

[39]  Alexandre Urzhumtsev,et al.  On the possibility of the observation of valence electron density for individual bonds in proteins in conventional difference maps. , 2004, Acta crystallographica. Section D, Biological crystallography.