Molecular modelling study of the 3D structure of the biglycan core protein, using homology modelling techniques

Dimitrios Vlachakis, Spyridon Champeris Tsaniras, Christos Feidakis, Sophia Kossida


Herein we report the establishment of the 3D structure of the biglycan core protein, using conventional homology molecular modelling techniques. The 3D model has been structurally optimised via molecular dynamics.  It was found that the final model of biglycan resembles in structure its template protein bearing a set of distinct parallel β-sheet structure patterns. The biglycan model bears a very hydrophobic amino acid region towards its inner cavity that acquires an arc-like structure. The external domain of the biglycan model is made up of hydrophilic residues that are exposed to the water solvent. It is those hydrophilic residues that are responsible for their interaction with polysaccharide polymers. Overall comparison of the model of biglycan to the recently determined x-ray structure of the same protein returns a very low Root Mean Square Deviation (RMSD), which confirms the viability of the model and its reliability as a platform for the study biglycan interactions.



Biglycan; dermatan sulphate; homology modelling; molecular dynamics simulation; small leucine reach proteins (SLRPs)


Aravind L & Koonin EV 1999 Gleaning non-trivial structural, functional and evolutionary information about proteins by iterative database searches. J Mol Biol 287 1023-1040

Balatsos N, Vlachakis D, Chatzigeorgiou V, Manta S, Komiotis D, Vlassi M & Stathopoulos C 2012 Kinetic and in silico analysis of the slow-binding inhibition of human poly (A)-specific ribonuclease (PARN) by novel nucleoside analogues Biochimie 94 214-221

Banerjee-Basu S & Baxevanis AD 2002 Predictive Methods Using Protein Sequences. In Bioinformatics: A Practical Guide to the Analysis of Genes and Proteins, edn 2. Eds AD Baxevanis & BFF Ouellette. New York, USA: John Wiley & Sons, Inc.

Berman HM, Battistuz T, Bhat TN, Bluhm WF, Bourne PE, Burkhardt K, Feng Z, Gilliland GL, Iype L, Jain S, Fagan P, Marvin J, Padilla D, Ravichandran V, Schneider B, Thanki N, Weissig H, Westbrook JD & Zardecki C 2002 The Protein Data Bank. Acta Crystallogr D Biol Crystallogr 58 899-907

Chen R, Li L & Weng Z 2003 ZDOCK: an initial-stage protein-docking algorithm. Proteins 52 80-87.

Chothia C 1992 One thousand families for the molecular biologists Nature 357 543-544

Chothia C & Lesk AM 1986 The relation between the divergence of sequence and structure in proteins EMBO J 5 823-826

Cintron C 1989 The function of proteoglycans in normal healing cornea. In Healing Processes in the Cornea. Eds CC Beuerman RW, Crosson CE & Kaufman HE. Texas: The Portfolio Publishing Company.

D'Alfonso G, Tramontano A & Lahm A 2001 Structural conservation in single-domain proteins: implications for homology modeling J Struct Biol 134 246-256

DeLano WL 2002 The PyMOL User's Manual. CA, USA: DeLano Scientific

Duan Y, Wu C, Chowdhury S, Lee MC, Xiong G, Zhang W, Yang R, Cieplak P, Luo R, Lee T, Caldwell J, Wang J & Kollman P 2003 A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. J Comput Chem 24 1999-2012

Eisenberg D, Lüthy R & Bowie JU 1997 VERIFY3D: assessment of protein models with three-dimensional profiles. Methods Enzymol 277 396-404

Funderburgh JL, Funderburgh ML, Mann MM, Corpuz L & Roth MR 2001 Proteoglycan expression during transforming growth factor beta -induced keratocyte-myofibroblast transdifferentiation. J Biol Chem 276 44173-44178

Funderburgh JL, Mann MM & Funderburgh ML 2003 Keratocyte phenotype mediates proteoglycan structure: a role for fibroblasts in corneal fibrosis J Biol Chem 278 45629-45637

Grishin NV 2001 Fold Change in Evolution of Protein Structures J Struct Biol 134 167-185

Hocking AM, Shinomura T & McQuillan DJ 1998 Leucine-Rich Repeat Glycoproteins of the Extracllular Matrix Matrix Biol 17 1-19

Krantz DD, Zidovetzki R, Kagan BL & Zipursky SL 1991 Amphipathic beta structure of a leucine-rich repeat peptide J Biol Chem 266 16801-16807

Kresse H, Liszio C, Schonherr E & Fisher LW 1997 Critical Role of Glutamate in a Central Leucine-rich Repeat of Decorin for Interaction with Type I Collagen J Biol Chem 272 18404-18410

Laskowski RA, Rullmannn JA, MacArthur MW, Kaptein R & Thornton JM 1996 AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR. J Biomol NMR 8 477-486

Li L, Chen R & Weng Z 2003 RDOCK: refinement of rigid-body protein docking predictions. Proteins 53 693-707.

Naito Z 2005 Role of the small leucine-rich proteoglycan (SLRP) family in pathological lesions and cancer cell growth J Nippon Med Sch 72 137-145

Palaiomylitou M, Tartas A, Vlachakis D, Tzamarias D & Vlassi M 2008 Investigating the structural stability of the Tup1‐interaction domain of Ssn6: Evidence for a conformational change on the complex Proteins 70 72-82

Sellis D, Drosou V, Vlachakis D, Voukkalis N, Giannakouros T & Vlassi M 2012 Phosphorylation of the arginine/serine repeats of lamin B receptor by SRPK1—Insights from molecular dynamics simulations. Biochim Biophys Acta 1820 44-55

Sellis D, Vlachakis D & Vlassi M 2009 Gromita: a fully integrated graphical user interface to gromacs 4 Bioinform Biol Insights 3 99-102

Schonherr E, Hausser H, Beavan L & Kresse H 1995 Decorin-type I collagen interaction. Presence of separate core protein-binding domains J Biol Chem 270 8877-8883.

Scott JE & Haigh M 1988 Identification of specific binding sites for keratan sulphate proteoglycans and chondroitin-dermatan sulphate proteoglycans on collagen fibrils in cornea by the use of cupromeronic blue in 'critical-electrolyte-concentration' techniques. Biochem J 253 607-610

Scott PG, Bishop PN & Bella J 2006a On the calculation of the binding force between decorin and collagen. J Biomech 39 1159-1160

Scott PG, Dodd CM, Bergmann EM, Sheehan JK & Bishop PN 2006b Crystal structure of the biglycan dimer and evidence that dimerisation is essential for folding and stability of class I small leucine rich repeat proteoglycans. J Biol Chem 281 13324-13332

Scott PG, McEwan PA, Dodd CM, Bergmann EM, Bishop PN & Bella J 2004 Crystal structure of the dimeric protein core of decorin, the archetypal small leucine-rich repeat proteoglycan Proc Natl Acad Sci U S A 101 15633-15638

Thompson JD, Higgins DG & Gibson TJ 1994 CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice Nucleic Acids Res 22 4673-4680

Vesentini S, Montevecchi FM & Redaelli A 2006 Response to letter to the editor: On the calculation of the binding force between decorin and collagen J Biomech 39 1160-1162

Vesentini S, Redaelli A & Montevecchi FM 2005 Estimation of the binding force of the collagen molecule-decorin core protein complex in collagen fibril J Biomech 38 433-443

Vangelatos I, Vlachakis D, Sophianopoulou V & Diallinas G 2009 Modelling and mutational evidence identify the substrate binding site and functional elements in APC amino acid transporters. Mol Membr Biol 26 356-370

Vlachakis D 2009 Theoretical study of the Usutu virus helicase 3D structure by means of computer-aided homology modelling. Theor Biol Med Model 6 9

Vlachakis D, Pavlopoulou A, Tsiliki G, Komiotis D, Stathopoulos C, Balatsos NA & Kossida S 2012 An integrated in silico approach to design specific inhibitors targeting human poly(a)-specific ribonuclease. PLoS One 7 e51113

Vlachakis D, Tsagrasoulis D, Megalooikonomou V & Kossida S 2013 Introducing Drugster: a comprehensive and fully integrated drug design, lead and structure optimization toolkit. Bioinformatics 29 126-128

Watson PG & Young RD 2004 Scleral structure, organisation and disease. A review Exp Eye Res 78 609-623

Weber IT, Harrison RW & Iozzo RV 1996 Model structure of decorin and implications for collagen fibrillogenesis J Biol Chem 271 31767-31770

Wegrowski Y, Paltot V, Gillery P, Kalis B, Randoux A & Maquart FX 1995 Stimulation of sulphated glycosaminoglycan and decorin production in adult dermal fibroblasts by recombinant human interleukin-4. Biochem J 307 673-678

Zubay G 1998 Biochemistry. Boston: McGraw Hill

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