Reconstruction of 3D Structures From Protein Contact Maps

Abstract

The prediction of the protein tertiary structure from solely its residue sequence (the so called Protein Folding Problem) is one of the most challenging problems in Structural Bioinformatics. We focus on the protein residue contact map. When this map is assigned it is possible to reconstruct the 3D structure of the protein backbone. The general problem of recovering a set of 3D coordinates consistent with some given contact map is known as a unit-disk-graph realization problem and it has been recently proven to be NP-Hard. In this paper we describe a heuristic method (COMAR) that is able to reconstruct with an unprecedented rate (3-15 seconds) a 3D model that exactly matches the target contact map of a protein. Working with a non-redundant set of 1760 proteins, we find that the scoring efficiency of finding a 3D model very close to the protein native structure depends on the threshold value adopted to compute the protein residue contact map. Contact maps whose threshold values range from 10 to 18 Angstroms allow reconstructing 3D models that are very similar to the proteins native structure.

Reconstruction of 3D Structures from Protein Contact Maps

“…The relation between contact map threshold, protein size, and protein 3D structure is analyzed, showing that on the average, contact maps computed at thresholds ranging from 10 to 18 A allow a better 3D structure recovery than those computed at lower values (ranging from 7 to 9 A). These results and a partial description of our algorithm already appeared in [19].…”

The LIBI Grid Platform for Bioinformatics

“…We have shown on a small protein set that FT-COMAR reconstruction is more tolerant to missing contacts than to added contacts in the contact map (Vassura, 2007b). We also introduced a pre-filtering procedure on noisy contact maps based on common neighbors.…”

“…any assortment of regular expression patterns, secondary structures and position weight matrices) and is HTC;  DNAFan (Gisel, 2004) searches specific genomic regions (DNA) defined by a Feature ANalyser where specific patterns can be matched by using PatSearch, hence it is HTC.  FT-COMAR (Vassura, 2007;Vassura, 2008) performs the reconstruction of 3D protein structure from its contact map. It is HTC;  AntiHunter (Lavorgna, 2005): tool for the identification of expressed sequence tag (EST) antisense transcripts from BLAST output.…”

“…Various heuristic algorithms have been proposed to solve the problem (Galaktionov, 1994;Vendruscolo, 1997;Bohr, 1993;Pollastri, 2006) but most of these methods have been tested only on the relative predictions and none of them are available to the scientific community. We have designed and implemented a new heuristic algorithm, called FT-COMAR, which can reconstruct the 3D structure of a protein from its contact map and which outperforms all existing algorithms (Vassura, 2007 a, b;Vassura, 2008). Grid technology is used to provide the processing power required to cope with the enormous computational effort that results when the effect of noise on the protein reconstruction is analyzed.…”

“…The "in GRID" extension FT-COMAR has been previously tested on a data set of 1,760 exact contact maps (Vassura, 2007a;Vassura, 2008) and on a subset of 120 erroneous contact maps (Vassura, 2007b). However a statistical validation should use a much larger data set.…”