The modelling of disulphides has been achieved by using the program called MODIP (MOdelling of DIsulphide bonds in Proteins)(Sowdhamini et al ., 1989) This database contains modelled as well as native disulphide bonds.These disulphide bonds are also graded based on stereochemical quality. For every protein, database provides a list of possible sites to introduce disulphide bonds along with their stereochemical grades.
This computer modelling program requires N,C alpha ,C beta coordinates as input and considers all possible residue pairs and calculate the C alpha-C alpha, C beta-C beta distances. It selects the residue pair with C alpha-C alpha distance of less than or equal to 6.5 Angstrom and C beta-C beta distance of less than or equal to 4.5 Angstrom and geometricaly fixes the sulfur atom and grades them based on the stereochemical quality.Click for the PDF file that describes the methodology and parameters used to calculate and grade pairs of residues.
Conformational parameters of Disulphide bond (Click on the image for full-size view)
Definition of various dihedral angles in Disulphide bond (Click on the image for full-size view)
Summary of MODIP procedure (Click on the image for full-size view)
Explanation of grade (Click on the image for full-size view)
Note: For the purpose of generating database relaxation in C alpha-C alpha , and C beta-C beta distances are included
C alpha-C alpha distance - 7 Angstrom C beta-C beta distance - 4.7 Angstrom
ReferencesR.Sowdhamini, N.Srinivasan, B.Shoichet, D.V.Santi, C.Ramakrishnan and P.Balaram (1989). Stereochemical modelling of disulfide bridges: Criteria for introduction into proteins by site-directed mutagenesis. Prot. Engng., 3, 95-103. N.Srinivasan, R.Sowdhamini, C.Ramakrishnan and P.Balaram (1990). Conformations of disulfide bridges in proteins and peptides. Int. J. Pept. Prot. Res., 36, 147-155. L.E.Donate, E.Gherardi, N.Srinivasan, R.Sowdhamini, S.Aparicio and T.L.Blundell (1994). Molecular evolution and domain structure of plasminogen-related growth factors (HGF/SF and HGFl/MSP). Prot. Sci., 3, 2378-2394. Zhou.H, Mazzulla.M.J, Kaufman.J.D, Stahl.S.J, Wingfield.P.T, Rubin.J.S, Bottaro.D.P and Byrd R.A (1998). The solution structure of the N-terminal domain of hepatocyte growth factor reveals a potential heparin-binding site. Structure., 6(1), 109-16. D.Y.Chirgadze, J.Hepple, R.A.Byrd, R.Sowdhamini and T.L.Blundell (1998). Insights into the structure of hepatocyte growth factor scatter factor (HGF/SF) and implications for receptor activation. FEBS Letts., 430, 126-129.]
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