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Open Access Highly Accessed Research article

Modeling of loops in proteins: a multi-method approach

Michal Jamroz and Andrzej Kolinski*

Author Affiliations

Laboratory of Theory of Biopolymers, Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland

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BMC Structural Biology 2010, 10:5  doi:10.1186/1472-6807-10-5

Published: 11 February 2010

Abstract

Background

Template-target sequence alignment and loop modeling are key components of protein comparative modeling. Short loops can be predicted with high accuracy using structural fragments from other, not necessairly homologous proteins, or by various minimization methods. For longer loops multiscale approaches employing coarse-grained de novo modeling techniques should be more effective.

Results

For a representative set of protein structures of various structural classes test predictions of loop regions have been performed using MODELLER, ROSETTA, and a CABS coarse-grained de novo modeling tool. Loops of various length, from 4 to 25 residues, were modeled assuming an ideal target-template alignment of the remaining portions of the protein. It has been shown that classical modeling with MODELLER is usually better for short loops, while coarse-grained de novo modeling is more effective for longer loops. Even very long missing fragments in protein structures could be effectively modeled. Resolution of such models is usually on the level 2-6 Å, which could be sufficient for guiding protein engineering. Further improvement of modeling accuracy could be achieved by the combination of different methods. In particular, we used 10 top ranked models from sets of 500 models generated by MODELLER as multiple templates for CABS modeling. On average, the resulting molecular models were better than the models from individual methods.

Conclusions

Accuracy of protein modeling, as demonstrated for the problem of loop modeling, could be improved by the combinations of different modeling techniques.