Improved dihedral-angle restraints for protein structure refinement

2003 ◽  
Vol 36 (1) ◽  
pp. 34-42 ◽  
Author(s):  
John P. Priestle
Keyword(s):  
High Resolution ◽  
Crystal Structures ◽  
Dihedral Angle ◽  
Small Molecule ◽  
Structure Refinement ◽  
Protein Structures ◽  
Dihedral Angles ◽  
Effective Number ◽  
Protein Structure Refinement ◽  
Crystal Contacts

Because of the relatively low-resolution diffraction of typical protein crystals, structure refinement is usually carried out employing stereochemical restraints to increase the effective number of observations. Well defined values for bond lengths and angles are available from small-molecule crystal structures. Such values do not exist for dihedral angles because of the concern that the strong crystal contacts in small-molecule crystal structures could distort the dihedral angles. This paper examines the dihedral-angle distributions in ultra-high-resolution protein structures (1.2 Å or better) as a means of analysing the population frequencies of dihedral angles in proteins and compares these with the stereochemical restraints currently used in one of the more widely used molecular-dynamics refinement packages,X-PLOR, and its successor,CNS. Discrepancies between the restraints used in these programs and what is actually seen in high-resolution protein structures are examined and an improved set of dihedral-angle restraint parameters are derived from these inspections.

scholarly journals Using more than 801 296 small-molecule crystal structures to aid in protein structure refinement and analysis

2017 ◽  
Vol 73 (3) ◽  
pp. 234-239 ◽  
Author(s):  
Jason C. Cole ◽  
Ilenia Giangreco ◽  
Colin R. Groom
Keyword(s):  
Protein Structure ◽  
Crystal Structures ◽  
Small Molecule ◽  
Structure Refinement ◽  
Three Dimensional ◽  
Paper Briefly ◽  
Ligand Complex ◽  
Protein Structure Refinement ◽  
Metal Organic ◽  
Structural Database

The Cambridge Structural Database (CSD) is the worldwide resource for the dissemination of all published three-dimensional structures of small-molecule organic and metal–organic compounds. This paper briefly describes how this collection of crystal structures can be used en masse in the context of macromolecular crystallography. Examples highlight how the CSD and associated software aid protein–ligand complex validation, and show how the CSD could be further used in the generation of geometrical restraints for protein structure refinement.

scholarly journals Using more than 801 296 small-molecule crystal structures to aid in protein structure refinement and analysis. Addendum

2017 ◽  
Vol 73 (12) ◽  
pp. 1029-1029
Author(s):  
Jason C. Cole ◽  
Ilenia Giangreco ◽  
Colin R. Groom
Keyword(s):  
Protein Structure ◽  
Crystal Structures ◽  
Small Molecule ◽  
Structure Refinement ◽  
Cambridge Structural Database ◽  
Acta Cryst ◽  
Protein Structure Refinement ◽  
Structure Solution ◽  
Structural Database

An addendum to theIntroductionof Coleet al.[(2017),Acta Cryst.D73, 234–239] is made to recognize the work of Bricogne, Smart and others in the development of methods to make use of Cambridge Structural Database data in protein structure solution.

scholarly journals Evaluating Unexpectedly Short Non-covalent Distances in X-ray Crystal Structures of Proteins with Electronic Structure Analysis

2019 ◽  
Author(s):  
Helena W. Qi ◽  
Heather Kulik
Keyword(s):  
Amino Acids ◽  
High Resolution ◽  
Crystal Structures ◽  
Close Contact ◽  
Protein Structures ◽  
Protein Crystal ◽  
X Ray ◽  
High Quality Protein ◽  
Van Der Waals Radii ◽  
Close Contacts

<div><div><div><p>We investigate unexpectedly short non-covalent distances (< 85% of the sum of van der Waals radii) in atomically resolved X-ray crystal structures of proteins. We curate over 13,000 high quality protein crystal structures and an ultra-high resolution (1.2 Å or better) subset containing > 1,000 structures. Although our non-covalent distance criterion excludes standard hydrogen bonds known to be essential in protein stability, we observe over 82,000 close contacts in the curated protein structures. Analysis of the frequency of amino acids participating in these interactions demonstrates some expected trends (i.e., enrichment of charged Lys, Arg, Asp, and Glu) but also reveals unexpected enhancement of Tyr in such interactions. Nearly all amino acids are observed to form at least one close contact with all other amino acids, and most interactions are preserved in the much smaller ultra high-resolution subset. We quantum-mechanically characterize the interaction energetics of a subset of > 6,000 close contacts with symmetry adapted perturbation theory to enable decomposition of interactions. We observe the majority of close contacts to be favorable. The shortest favorable non-covalent distances are under 2.2 Å and are very repulsive when characterized with classical force fields. This analysis reveals stabilization by a combination of electrostatic and charge transfer effects between hydrophobic (i.e., Val, Ile, Leu) amino acids and charged Asp or Glu. We also observe a unique hydrogen bonding configuration between Tyr and Asn/Gln involving both residues acting simultaneously as hydrogen bond donors and acceptors. This work confirms the importance of first-principles simulation in explaining unexpected geometries in protein crystal structures.</p></div></div></div>

scholarly journals Crystal structures and Hirshfeld surface analysis of a series of 4-O-arylperfluoropyridines

2019 ◽  
Vol 75 (8) ◽  
pp. 1102-1107 ◽  
Author(s):  
Andrew J. Peloquin ◽  
Cynthia A. Corley ◽  
Sonya K. Adas ◽  
Gary J. Balaich ◽  
Scott T. Iacono
Keyword(s):  
Crystal Structures ◽  
Aromatic Ring ◽  
Dihedral Angle ◽  
Surface Analysis ◽  
Phenyl Ring ◽  
Pyridine Ring ◽  
Hirshfeld Surface ◽  
Hirshfeld Surface Analysis ◽  
Dihedral Angles ◽  
Twofold Axis

Five new crystal structures of perfluoropyridine substituted in the 4-position with phenoxy, 4-bromophenoxy, naphthalen-2-yloxy, 6-bromonaphthalen-2-yloxy, and 4,4′-biphenoxy are reported, viz. 2,3,5,6-tetrafluoro-4-phenoxypyridine, C11H5F4NO (I), 4-(4-bromophenoxy)-2,3,5,6-tetrafluoropyridine, C11H4BrF4NO (II), 2,3,5,6-tetrafluoro-4-[(naphthalen-2-yl)oxy]pyridine, C15H7F4NO (III), 4-[(6-bromonaphthalen-2-yl)oxy]-2,3,5,6-tetrafluoropyridine, C15H6BrF4NO (IV), and 2,2′-bis[(perfluoropyridin-4-yl)oxy]-1,1′-biphenyl, C22H8F8N2O2 (V). The dihedral angles between the aromatic ring systems in I–IV are 78.74 (8), 56.35 (8), 74.30 (7), and 64.34 (19)°, respectively. The complete molecule of V is generated by a crystallographic twofold axis: the dihedral angle between the pyridine ring and adjacent phenyl ring is 80.89 (5)° and the equivalent angle between the biphenyl rings is 27.30 (5)°. In each crystal, the packing is driven by C—H...F interactions, along with a variety of C—F...π, C—H...π, C—Br...N, C—H...N, and C—Br...π contacts. Hirshfeld surface analysis was conducted to aid in the visualization of these various influences on the packing.

ACMS: a database of alternate conformations found in the atoms of main and side chains of protein structures

2019 ◽  
Vol 52 (4) ◽  
pp. 910-913 ◽  
Author(s):  
R. Santhosh ◽  
P. Chandrasekaran ◽  
Daliah Michael ◽  
K. Rangachari ◽  
Namrata Bankoti ◽  
...  
Keyword(s):  
High Resolution ◽  
Knowledge Base ◽  
Crystal Structures ◽  
Protein Structures ◽  
Protein Molecule ◽  
Data Bank ◽  
Side Chain ◽  
Biological Macromolecules ◽  
Conformational Ensembles ◽  
User Friendly

Proteins are usually dynamic biological macromolecules, thereby exhibiting a large number of conformational ensembles which influence the association with their neighbours and interacting partners. Most of the side-chain atoms and a few main-chain atoms of the high-resolution crystal structures deposited in the Protein Data Bank adopt alternate conformations. This kind of conformational behaviour prompted the authors to explore the relationship, if any, between the alternate conformations and the function of the protein molecule. Thus, a knowledge base of the alternate conformations of the main- and side-chain atoms of protein structures has been developed. It provides a detailed description of the alternate conformations of various residues for more than 60 000 high-resolution crystal structures. The proposed knowledge base is very user friendly and has various flexible options. The knowledge base will be updated periodically and can be accessed at http://iris.physics.iisc.ac.in/acms.

scholarly journals A Second Look at the Crystal Structures of Drosophila melanogaster Acetylcholinesterase in Complex with Tacrine Derivatives Provides Insights Concerning Catalytic Intermediates and the Design of Specific Insecticides

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1198 ◽  
Author(s):  
Florian Nachon ◽  
Terrone L. Rosenberry ◽  
Israel Silman ◽  
Joel L. Sussman
Keyword(s):  
Drosophila Melanogaster ◽  
Crystal Structures ◽  
Small Molecule ◽  
Diffraction Data ◽  
Active Site ◽  
Structure Refinement ◽  
Second Look ◽  
Density Maps ◽  
Original Analysis ◽  
Public Data

Over recent decades, crystallographic software for data processing and structure refinement has improved dramatically, resulting in more accurate and detailed crystal structures. It is, therefore, sometimes valuable to have a second look at “old” diffraction data, especially when earlier interpretation of the electron density maps was rather difficult. Here, we present updated crystal structures of Drosophila melanogaster acetylcholinesterase (DmAChE) originally published in [Harel et al., Prot Sci (2000) 9:1063-1072], which reveal features previously unnoticed. Thus, previously unmodeled density in the native active site can be interpreted as stable acetylation of the catalytic serine. Similarly, a strong density in the DmAChE/ZA complex originally attributed to a sulfate ion is better interpreted as a small molecule that is covalently bound. This small molecule can be modeled as either a propionate or a glycinate. The complex is reminiscent of the carboxylate butyrylcholinesterase complexes observed in crystal structures of human butyrylcholinesterases from various sources, and demonstrates the remarkable ability of cholinesterases to stabilize covalent complexes with carboxylates. A very strong peak of density (10 σ) at covalent distance from the Cβ of the catalytic serine is present in the DmAChE/ZAI complex. This can be undoubtedly attributed to an iodine atom, suggesting an unanticipated iodo/hydroxyl exchange between Ser238 and the inhibitor, possibly driven by the intense X-ray irradiation. Finally, the binding of tacrine-derived inhibitors, such as ZA (1DX4) or the iodinated analog, ZAI (1QON) results in the appearance of an open channel that connects the base of the active-site gorge to the solvent. This channel, which arises due to the absence of the conserved tyrosine present in vertebrate cholinesterases, could be exploited to design inhibitors specific to insect cholinesterases. The present study demonstrates that updated processing of older diffraction images, and the re-refinement of older diffraction data, can produce valuable information that could not be detected in the original analysis, and strongly supports the preservation of the diffraction images in public data banks.

scholarly journals Crystal structures of (E)-(3-ethyl-1-methyl-2,6-diphenylpiperidin-4-ylidene)amino phenyl carbonate and (E)-(3-isopropyl-1-methyl-2,6-diphenylpiperidin-4-ylidene)amino phenyl carbonate

2014 ◽  
Vol 70 (10) ◽  
pp. 199-202 ◽  
Author(s):  
B. Raghuvarman ◽  
R. Sivakumar ◽  
V. Thanikachalam ◽  
S. Aravindhan
Keyword(s):  
Hydrogen Bonds ◽  
Crystal Structures ◽  
Dihedral Angle ◽  
Intermolecular Interactions ◽  
Three Dimensional ◽  
Piperidine Ring ◽  
Dihedral Angles ◽  
Π Interactions ◽  
Dimensional Network ◽  
Phenyl Rings

In the title compounds, C27H28N2O3, (I), and C28H30N2O3, (II), the conformation about the C=N bond isE. The piperidine rings adopt chair conformations with the attached phenyl rings almost normal to their mean planes, the dihedral angles being 85.82 (8) and 85.84 (7)° in (I), and 87.98 (12) and 86.42 (13)° in (II). The phenyl rings are inclined to one another by 52.87 (8)° in (I) and by 60.51 (14)° in (II). The main difference in the conformation of the two compounds is the angle of inclination of the phenoxycarbonyl ring to the piperidine ring mean plane. In (I), these two planes are almost coplanar, with a dihedral angle of 2.05 (8)°, while in (II), this angle is 45.24 (13)°. In the crystal of (I), molecules are linked by C—H...O hydrogen bonds, forming inversion dimers withR22(14) loops. The dimers are linkedviaC—H...π interactions forming a three-dimensional network. In the crystal of (II), there are no significant intermolecular interactions present.

1,1´,3,3´-Tetramethyl-2,2´-diimidazolium dication: Its bromide salt and the tetraphenylborates of its ketone adducts

2000 ◽  
Vol 215 (1) ◽  
Author(s):  
H. Bock ◽  
N. Nagel ◽  
P. Eller
Keyword(s):  
Least Squares ◽  
Crystal Structures ◽  
Dihedral Angle ◽  
Crystal Engineering ◽  
Low Temperatures ◽  
Conformational Flexibility ◽  
Semiempirical Calculations ◽  
Dihedral Angles ◽  
Packing Effects ◽  
Borate Salts

The crystal structures of several 1,1´,3,3´-tetramethyl-2,2´-diimidazolium dication salts were determined at low temperatures. The dihedral angles between the planes of the two five-membered rings vary between 64° in the bromide salt and up to 80° in the ketone adduct tetraphenylborates, indicating some conformational flexibility around the central C–C bond of the 1,1´,3,3´-tetramethyl-2,2´-diimidazolium dication. Semiempirical calculations predict the conformation with a dihedral angle of 90° to be most favourable and the conformations within the crystal structures to be results of packing effects. In tetra phenyl borate salts of ketone and diketone adducts, the oxygen centers coordinate to the dication from above as well as below the defined molecular least squares plane and form chains of alternating dications and ketones. Since this packing motif is found in tetraphenylborate salts with different ketones, it might prove to be a robust supramolecular synthone in crystal engineering.

Experimental assessment of differences between related protein crystal structures

1999 ◽  
Vol 55 (11) ◽  
pp. 1878-1884 ◽  
Author(s):  
Gerard J. Kleywegt
Keyword(s):  
Crystal Structures ◽  
Electron Density ◽  
Local Density ◽  
Structure Refinement ◽  
Protein Structures ◽  
Biological Significance ◽  
Protein Crystal ◽  
Related Protein ◽  
Density Correlation ◽  
Experimental Electron Density

Prior to attaching any biological significance to differences between two related protein crystal structures, it must be established that such differences are genuine, rather than artefacts of the structure-determination protocol. This will be all the more important as more and more related protein structures are solved and comparative structural biology attempts to correlate structural differences with variations in biological function, activity or affinity. A method has been developed which enables unbiased assessment of differences between the structures of related biomacromolecules using experimental crystallographic information alone. It is based on the use of local density-correlation maps, which contain information regarding the similarity of the experimental electron density for corresponding parts of different copies of a molecule. The method can be used to assess a priori which parts of two or more molecules are likely to be structurally similar; this information can then be employed during structure refinement. Alternatively, the method can be used a posteriori to verify that differences observed in two or more models are supported by the experimental information. Several examples are discussed which validate the notion that local conformational variability is highly correlated to differences in the local experimental electron density.

scholarly journals CIF Applications. XI.A La Mode: a ligand and monomer object data environment. I. Automated construction of mmCIF monomer and ligand models

1999 ◽  
Vol 32 (1) ◽  
pp. 125-133 ◽  
Author(s):  
Les Clowney ◽  
John D. Westbrook ◽  
Helen M. Berman
Keyword(s):  
High Resolution ◽  
Crystal Structures ◽  
Small Molecule ◽  
Chemical Component ◽  
Chemical Components ◽  
Comprehensive Description ◽  
Information File ◽  
Data Environment ◽  
Component Models ◽  
Mode A

The macromolecular Crystallographic Information File (mmCIF) dictionary [Fitzgeraldet al.(1997).The Macromolecular Crystallographic Information File Dictionary, http://ndbserver.rutgers.edu/mmcif] provides a comprehensive description of chemical components used as models in the crystallographic refinement of macromolecular structures. A new ligand and monomer object data environment namedA La Modeis described for building chemical-component models in the mmCIF representation from surveys of high-resolution small-molecule crystal structures. Examples of the application of this system are presented for an intercalating drug component and for a nucleotide unit constructed from independent base, sugar and phosphate components.

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