Structure validation: Difference between revisions

Revision as of 17:41, 13 August 2023

Revision as of 17:45, 13 August 2023

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==== Packing and Electrostatics: globular proteins ====

For globular proteins, interior atomic packing (arising from short-range, local interactions) of side-chains<ref>{{Cite journal| vauthors = Shen MY, Davis FP, Sali A |date= March 2005|title=The optimal size of a globular protein ___domain: A simple sphere-packing model|journal=Chemical Physics Letters|volume=405|issue=1–3|pages=224–228|doi=10.1016/j.cplett.2005.02.029|issn=0009-2614|bibcode= 2005CPL...405..224S}}</ref><ref>{{cite journal | vauthors = Misura KM, Morozov AV, Baker D | title = Analysis of anisotropic side-chain packing in proteins and application to high-resolution structure prediction | journal = Journal of Molecular Biology | volume = 342 | issue = 2 | pages = 651–64 | date = September 2004 | pmid = 15327962 | doi = 10.1016/j.jmb.2004.07.038 }}</ref><ref>{{cite journal | vauthors = Basu S, Bhattacharyya D, Banerjee R | title = Mapping the distribution of packing topologies within protein interiors shows predominant preference for specific packing motifs | journal = BMC Bioinformatics | volume = 12 | issue = 1 | pages = 195 | date = May 2011 | pmid = 21605466 | pmc = 3123238 | doi = 10.1186/1471-2105-12-195 | doi-access = free }}</ref><ref name="The jigsaw puzzle model: search for">{{cite journal | vauthors = Banerjee R, Sen M, Bhattacharya D, Saha P | title = The jigsaw puzzle model: search for conformational specificity in protein interiors | journal = Journal of Molecular Biology | volume = 333 | issue = 1 | pages = 211–26 | date = October 2003 | pmid = 14516754 | doi = 10.1016/j.jmb.2003.08.013 }}</ref> has been shown to be pivotal in the structural stabilization of the protein-fold. On the other hand, the electrostatic harmony (non-local, long-range) of the overall fold<ref name=":2">{{cite journal | vauthors = Basu S, Bhattacharyya D, Banerjee R | title = Self-complementarity within proteins: bridging the gap between binding and folding | journal = Biophysical Journal | volume = 102 | issue = 11 | pages = 2605–14 | date = June 2012 | pmid = 22713576 | pmc = 3368132 | doi = 10.1016/j.bpj.2012.04.029 | bibcode = 2012BpJ...102.2605B }}</ref> has also been shown to be essential for its stabilization. Packing anomalies include steric clashes,<ref>{{cite journal | vauthors = Chen VB, Arendall WB, Headd JJ, Keedy DA, Immormino RM, Kapral GJ, Murray LW, Richardson JS, Richardson DC | display-authors = 6 | title = MolProbity: all-atom structure validation for macromolecular crystallography | journal = Acta Crystallographica Section D | volume = 66 | issue = Pt 1 | pages = 12–21 | date = January 2010 | pmid = 20057044 | pmc = 2803126 | doi = 10.1107/S0907444909042073 }}</ref> short contacts,<ref name="The jigsaw puzzle model: search for"/> holes<ref>{{cite journal | vauthors = Sheffler W, Baker D | title = RosettaHoles: rapid assessment of protein core packing for structure prediction, refinement, design, and validation | journal = Protein Science | volume = 18 | issue = 1 | pages = 229–39 | date = January 2009 | pmid = 19177366 | pmc = 2708028 | doi = 10.1002/pro.8 }}</ref> and cavities<ref>{{cite journal | vauthors = Chakravarty S, Varadarajan R | title = Residue depth: a novel parameter for the analysis of protein structure and stability | journal = Structure | volume = 7 | issue = 7 | pages = 723–32 | date = July 1999 | pmid = 10425675 | doi = 10.1016/s0969-2126(99)80097-5 | doi-access = free }}</ref> while electrostatic disharmony<ref name=":2" /><ref>{{cite journal | vauthors = Basu S, Bhattacharyya D, Banerjee R | title = Applications of complementarity plot in error detection and structure validation of proteins | journal = Indian Journal of Biochemistry & Biophysics | volume = 51 | issue = 3 | pages = 188–200 | date = June 2014 | pmid = 25204080 }}</ref> refer to unbalanced partial charges in the protein core (particularly relevant for designed protein interiors). While the clash-score of [http://molprobity.biochem.duke.edu/ Molprobity] identifies steric clashes at a very high resolution, the [[Complementarity plot|Complementarity Plot]] combines packing anomalies with electrostatic imbalance of side-chains and signals for either or both.

====Carbohydrates====

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The branched and cyclic nature of carbohydrates poses particular problems to structure validation tools.<ref>{{cite journal | vauthors = Agirre J, Davies GJ, Wilson KS, Cowtan KD | title = Carbohydrate structure: the rocky road to automation | journal = Current Opinion in Structural Biology | volume = 44 | pages = 39–47 | date = June 2017 | pmid = 27940408 | doi = 10.1016/j.sbi.2016.11.011 | url = http://eprints.whiterose.ac.uk/109296/1/COStBi_postprint.pdf | series = Carbohydrates • Sequences and topology }}</ref> At higher resolutions, it is possible to determine the sequence/structure of oligo- and poly-saccharides, both as covalent modifications and as ligands. However, at lower resolutions (typically lower than 2.0Å), sequences/structures should either match known structures, or be supported by complementary techniques such as Mass Spectrometry.<ref>{{cite journal | vauthors = Crispin M, Stuart DI, Jones EY | title = Building meaningful models of glycoproteins | journal = Nature Structural & Molecular Biology | volume = 14 | issue = 5 | pages = 354; discussion 354–5 | date = May 2007 | pmid = 17473875 | doi = 10.1038/nsmb0507-354a | s2cid = 2020697 | doi-access = free }}</ref> Also, monosaccharides have clear conformational preferences (saturated rings are typically found in chair conformations),<ref>{{cite journal | vauthors = Davies GJ, Planas A, Rovira C | title = Conformational analyses of the reaction coordinate of glycosidases | journal = Accounts of Chemical Research | volume = 45 | issue = 2 | pages = 308–16 | date = February 2012 | pmid = 21923088 | doi = 10.1021/ar2001765 }}</ref> but errors introduced during model building and/or refinement (wrong linkage chirality or distance, or wrong choice of model - see<ref>{{cite journal | vauthors = Agirre J | title = Strategies for carbohydrate model building, refinement and validation | journal = Acta Crystallographica Section D | volume = 73 | issue = Pt 2 | pages = 171–186 | date = February 2017 | pmid = 28177313 | pmc = 5297920 | doi = 10.1107/S2059798316016910 | url = http://journals.iucr.org/d/issues/2017/02/00/ba5257/ }}</ref> for recommendations on carbohydrate model building and refinement and<ref>{{cite journal | vauthors = Lütteke T | title = Analysis and validation of carbohydrate three-dimensional structures | journal = Acta Crystallographica Section D | volume = 65 | issue = Pt 2 | pages = 156–68 | date = February 2009 | pmid = 19171971 | pmc = 2631634 | doi = 10.1107/S0907444909001905 }}</ref><ref>{{cite book | vauthors = Lütteke T, von der Lieth CW | title = Glycomics | chapter = Data mining the PDB for glyco-related data | series = Methods in Molecular Biology | volume = 534 | pages = 293–310 | date = 2009-01-01 | pmid = 19277543 | doi = 10.1007/978-1-59745-022-5_21 | isbn = 978-1-58829-774-7 }}</ref><ref>{{cite journal | vauthors = Joosten RP, Lütteke T | title = Carbohydrate 3D structure validation | journal = Current Opinion in Structural Biology | volume = 44 | pages = 9–17 | date = June 2017 | pmid = 27816840 | doi = 10.1016/j.sbi.2016.10.010 | url = http://eprints.whiterose.ac.uk/109296/1/COStBi_postprint.pdf }}</ref> for reviews on general errors in carbohydrate structures) can bring their atomic models out of their energy minima. Around 20% of the deposited carbohydrate structures are in unjustified energy minima.<ref>{{cite journal | vauthors = Agirre J, Davies G, Wilson K, Cowtan K | title = Carbohydrate anomalies in the PDB | journal = Nature Chemical Biology | volume = 11 | issue = 5 | pages = 303 | date = May 2015 | pmid = 25885951 | doi = 10.1038/nchembio.1798 | url = http://eprints.whiterose.ac.uk/95242/1/AgirreDaviesWIlsonCowtan_self_archived.pdf | doi-access = free }}</ref>

A number of carbohydrate validation web services are available at [http://ww.glycosciences.de glycosciences.de] (including nomenclature checks and linkage checks by [http://www.glycosciences.de/tools/pdb-care/ pdb-care],<ref>{{cite journal | vauthors = Lütteke T, von der Lieth CW | title = pdb-care (PDB carbohydrate residue check): a program to support annotation of complex carbohydrate structures in PDB files | journal = BMC Bioinformatics | volume = 5 | pages = 69 | date = June 2004 | pmid = 15180909 | pmc = 441419 | doi = 10.1186/1471-2105-5-69 | doi-access = free }}</ref> and cross-validation with Mass Spectrometry data through the use of GlycanBuilder), whereas the [http://www.ccp4.ac.uk CCP4] suite currently distributes [http://www.ccp4.ac.uk/html/privateer.html Privateer],<ref name=":0">{{cite journal | vauthors = Agirre J, Iglesias-Fernández J, Rovira C, Davies GJ, Wilson KS, Cowtan KD | title = Privateer: software for the conformational validation of carbohydrate structures | journal = Nature Structural & Molecular Biology | volume = 22 | issue = 11 | pages = 833–4 | date = November 2015 | pmid = 26581513 | doi = 10.1038/nsmb.3115 | s2cid = 33800088 | url = http://eprints.whiterose.ac.uk/95794/1/Privateer_selfarchived.pdf }}</ref> which is a tool that is integrated into the model building and refinement process itself. Privateer is able to check stereo- and regio-chemistry, ring conformation and puckering, linkage torsions, and real-space correlation against positive omit density, generating aperiodic torsion restraints on ring bonds, which can be used by any refinement software in order to maintain the monosaccharide's minimal energy conformation.<ref name=":0" />

Privateer also generates scalable two-dimensional SVG diagrams according to the Essentials of Glycobiology<ref name=":1">{{cite journal | vauthors = Varki A, Cummings RD, Aebi M, Packer NH, Seeberger PH, Esko JD, Stanley P, Hart G, Darvill A, Kinoshita T, Prestegard JJ, Schnaar RL, Freeze HH, Marth JD, Bertozzi CR, Etzler ME, Frank M, Vliegenthart JF, Lütteke T, Perez S, Bolton E, Rudd P, Paulson J, Kanehisa M, Toukach P, Aoki-Kinoshita KF, Dell A, Narimatsu H, York W, Taniguchi N, Kornfeld S | display-authors = 6 | title = Symbol Nomenclature for Graphical Representations of Glycans | journal = Glycobiology | volume = 25 | issue = 12 | pages = 1323–4 | date = December 2015 | pmid = 26543186 | pmc = 4643639 | doi = 10.1093/glycob/cwv091 }}</ref> standard symbol nomenclature containing all the validation information as tooltip annotations (see figure). This functionality is currently integrated into other CCP4 programs, such as the molecular graphics program CCP4mg (through the ''Glycoblocks'' 3D representation,<ref>{{cite journal | vauthors = McNicholas S, Agirre J | title = Glycoblocks: a schematic three-dimensional representation for glycans and their interactions | journal = Acta Crystallographica Section D | volume = 73 | issue = Pt 2 | pages = 187–194 | date = February 2017 | pmid = 28177314 | pmc = 5297921 | doi = 10.1107/S2059798316013553 }}</ref> which conforms to the standard symbol nomenclature<ref name=":1" />) and the suite's graphical interface, CCP4i2.