Structure validation: Difference between revisions

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Though, mRNA structures are generally short-lived and single-stranded, there are an abundance of non-coding RNAs with different secondary and tertiary folding (tRNA, rRNA etc.) which contain a preponderance of the canonical [[Base pair|Watson-Crick]] (WC) base-pairs, together with significant number of non-Watson Crick (NWC) base-pairs - for which such RNA also qualify for regular structural validation that apply for nucleic acid helices. The standard practice is to analyse the intra- (Transnational: Shift, Slide, Rise; Rotational: Tilt, Roll, Twist) and inter-base-pair geometrical parameters (Transnational: Shear, Stagger, Stretch, Rotational: Buckle, Propeller, Opening) - whether in-range or out-of-range with respect to their suggested values <ref>{{Cite journal|last=Dickerson|first=Richard E.|date=1989-02-01|title=Definitions and Nomenclature of Nucleic Acid Structure Parameters|url=https://doi.org/10.1080/07391102.1989.10507726|journal=Journal of Biomolecular Structure and Dynamics|volume=6|issue=4|pages=627–634|doi=10.1080/07391102.1989.10507726|issn=0739-1102|pmid=2619931}}</ref><ref>{{Cite journal|last=Olson|first=Wilma K|last2=Bansal|first2=Manju|last3=Burley|first3=Stephen K|last4=Dickerson|first4=Richard E|last5=Gerstein|first5=Mark|last6=Harvey|first6=Stephen C|last7=Heinemann|first7=Udo|last8=Lu|first8=Xiang-Jun|last9=Neidle|first9=Stephen|last10=Shakked|first10=Zippora|last11=Sklenar|first11=Heinz|date=2001-10-12|title=A standard reference frame for the description of nucleic acid base-pair geometry11Edited by P. E. Wright22This is a document of the Nomenclature Committee of IUBMB (NC-IUBMB)/IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (JCBN), whose members are R. Cammack (chairman), A. Bairoch, H.M. Berman, S. Boyce, C.R. Cantor, K. Elliott, D. Horton, M. Kanehisa, A. Kotyk, G.P. Moss, N. Sharon and K.F. Tipton.|url=http://www.sciencedirect.com/science/article/pii/S0022283601949873|journal=Journal of Molecular Biology|language=en|volume=313|issue=1|pages=229–237|doi=10.1006/jmbi.2001.4987|issn=0022-2836}}</ref>. These parameters describe the relative orientations of the two paired bases with respect to each other in two strands (intra) along with those of the two stacked base pairs (inter) with respect to each other, and, hence, together, they serve to validate nucleic acid structures in general. Since, RNA-helices are small in length (average: 10-20 bps), the use of electrostatic surface potential as a validation parameter <ref>{{Cite journal|last=Bhattacharyya|first=Dhananjay|last2=Halder|first2=Sukanya|last3=Basu|first3=Sankar|last4=Mukherjee|first4=Debasish|last5=Kumar|first5=Prasun|last6=Bansal|first6=Manju|date=2017-01-19|title=RNAHelix: computational modeling of nucleic acid structures with Watson–Crick and non-canonical base pairs|url=http://dx.doi.org/10.1007/s10822-016-0007-0|journal=Journal of Computer-Aided Molecular Design|volume=31|issue=2|pages=219–235|doi=10.1007/s10822-016-0007-0|issn=0920-654X}}</ref> has been found to be beneficial, particularly for modelling purposes.

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

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====Packing and Electrostatics ====

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 }}</ref><ref>{{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, Biological Crystallography | volume = 66 | issue = Pt 1 | pages = 12–21 | date = January 2010 | pmid = 20057044 | pmc = 2803126 | doi = 10.1107/S0907444909042073 }}</ref>, short contacts<ref>{{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>, 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 }}</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.