Modelling multiple disulphide loop containing polypeptides by random conformation generation. The test cases of α-conotoxin GI and edothelin I

Sowdhamini, R and Ramakrishnan, C and Balaram, P (1993) Modelling multiple disulphide loop containing polypeptides by random conformation generation. The test cases of α-conotoxin GI and edothelin I. In: Protein Engineering, 6 (8). pp. 873-882.

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Abstract

A general procedure for arriving at 3-D models of disulphiderich olypeptide systems based on the covalent cross-link constraints has been developed. The procedure, which has been coded as a computer program, RANMOD, assigns a large number of random, permitted backbone conformations to the polypeptide and identifies stereochemically acceptable structures as plausible models based on strainless disulphide bridge modelling. Disulphide bond modelling is performed using the procedure MODIP developed earlier, in connection with the choice of suitable sites where disulphide bonds could be engineered in proteins (Sowdhamini,R., Srinivasan,N., Shoichet,B., Santi,D.V., Ramakrishnan,C. and Balaram,P. (1989) Protein Engng, 3, 95-103). The method RANMOD has been tested on small disulphide loops and the structures compared against preferred backbone conformations derived from an analysis of putative disulphide subdatabase and model calculations. RANMOD has been applied to disulphiderich peptides and found to give rise to several stereochemically acceptable structures. The results obtained on the modelling of two test cases, a-conotoxin GI and endothelin I, are presented. Available NMR data suggest that such small systems exhibit conformational heterogeneity in solution. Hence, this approach for obtaining several distinct models is particularly attractive for the study of conformational excursions.

Item Type:	Journal Article
Publication:	Protein Engineering
Publisher:	Oxford University Press
Additional Information:	Copyright of this article belongs to Oxford University Press.
Keywords:	a-conotoxin Gl;disulphide bond modelling;disulphide- rich polypeptide systems;endothelin
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	17 Feb 2011 07:39
Last Modified:	17 Feb 2011 07:39
URI:	http://eprints.iisc.ac.in/id/eprint/35617

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