ePrints@IIScePrints@IISc Home | About | Browse | Latest Additions | Advanced Search | Contact | Help

MODIP revisited: re-evaluation and refinement of an automated procedure for modeling of disulfide bonds in proteins

Dani, Vardhan S and Ramakrishnan, C and Varadarajan, Raghavan (2003) MODIP revisited: re-evaluation and refinement of an automated procedure for modeling of disulfide bonds in proteins. In: Protein Engineering,, 16 (3). pp. 187-193.

[img] PDF
187.pdf - Published Version
Restricted to Registered users only

Download (179Kb) | Request a copy
Official URL: http://peds.oxfordjournals.org/cgi/reprint/16/3/18...

Abstract

There have been several attempts to stabilize proteins through the introduction of engineered disulfide bonds. For reasons that are currently unclear, these have met with mixed success. Hence identification of locations where introduction of a disulfide cross-link will lead to protein stabilization is still a challenging task. A computational procedure, MODIP, was introduced more than a decade ago to select sites in protein structures that have the correct geometry for disulfide formation when replaced by Cys. In this study, we re-evaluated the stereochemical criteria used by MODIP for the selection and gradation of sites for modeling disulfides. We introduced steric criteria to check for energetically unfavorable non-bonded contacts with the modeled disulfide, since these can considerably offset the stabilizing effect of the cross-link. The performance of the refined procedure was checked for its ability to correctly predict naturally occurring disulfide bonds in proteins. A set of proteins in which disulfide bonds were introduced experimentally were analyzed with respect to MODIP predictions, stability and other parameters such as accessibility, residue depth, B-factors of the mutated sites, change in volume upon mutation and loop length enclosed by the disulfide. The analysis suggests that in addition to proper stereochemistry, stabilizing disulfides occur in regions of low depth, relatively high mobility, have a loop length greater than 25 and where the disulfide typically occupies a volume less than or equal to that of the original residues.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Oxford University Press.
Keywords: disulfide bonds;protein stability;site-directed mutagenesis.
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 24 Nov 2009 07:38
Last Modified: 19 Sep 2010 04:55
URI: http://eprints.iisc.ernet.in/id/eprint/17139

Actions (login required)

View Item View Item