Dataset Information

Alignment of distantly related protein structures: algorithm, bound and implications to homology modeling.

ABSTRACT: Building an accurate alignment of a large set of distantly related protein structures is still very challenging.This article presents a novel method 3DCOMB that can generate a multiple structure alignment (MSA) with not only as many conserved cores as possible, but also high-quality pairwise alignments. 3DCOMB is unique in that it makes use of both local and global structure environments, combined by a statistical learning method, to accurately identify highly similar fragment blocks (HSFBs) among all proteins to be aligned. By extending the alignments of these HSFBs, 3DCOMB can quickly generate an accurate MSA without using progressive alignment. 3DCOMB significantly excels others in aligning distantly related proteins. 3DCOMB can also generate correct alignments for functionally similar regions among proteins of very different structures while many other MSA tools fail. 3DCOMB is useful for many real-world applications. In particular, it enables us to find out that there is still large improvement room for multiple template homology modeling while several other MSA tools fail to do so.3DCOMB is available at http://ttic.uchicago.edu/~jinbo/software.htm.jinboxu@gmail.comSupplementary data are available at Bioinformatics online.

SUBMITTER: Wang S

PROVIDER: S-EPMC3167051 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Alignment of distantly related protein structures: algorithm, bound and implications to homology modeling.

Wang Sheng S Peng Jian J Xu Jinbo J

Bioinformatics (Oxford, England) 20110726 18

<h4>Motivation</h4>Building an accurate alignment of a large set of distantly related protein structures is still very challenging.<h4>Results</h4>This article presents a novel method 3DCOMB that can generate a multiple structure alignment (MSA) with not only as many conserved cores as possible, but also high-quality pairwise alignments. 3DCOMB is unique in that it makes use of both local and global structure environments, combined by a statistical learning method, to accurately identify highly ...[more]

PMID: 21791532

Similar Datasets

Project description:BackgroundLipocalins are widely distributed in nature and are found in bacteria, plants, arthropoda and vertebra. In hematophagous arthropods, they are implicated in the successful accomplishment of the blood meal, interfering with platelet aggregation, blood coagulation and inflammation and in the transmission of disease parasites such as Trypanosoma cruzi and Borrelia burgdorferi. The pairwise sequence identity is low among this family, often below 30%, despite a well conserved tertiary structure. Under the 30% identity threshold, alignment methods do not correctly assign and align proteins. The only safe way to assign a sequence to that family is by experimental determination. However, these procedures are long and costly and cannot always be applied. A way to circumvent the experimental approach is sequence and structure analyze. To further help in that task, the residues implicated in the stabilisation of the lipocalin fold were determined. This was done by analyzing the conserved interactions for ten lipocalins having a maximum pairwise identity of 28% and various functions.ResultsIt was determined that two hydrophobic clusters of residues are conserved by analysing the ten lipocalin structures and sequences. One cluster is internal to the barrel, involving all strands and the 310 helix. The other is external, involving four strands and the helix lying parallel to the barrel surface. These clusters are also present in RaHBP2, a unusual "outlier" lipocalin from tick Rhipicephalus appendiculatus. This information was used to assess assignment of LIR2 a protein from Ixodes ricinus and to build a 3D model that helps to predict function. FTIR data support the lipocalin fold for this protein.ConclusionBy sequence and structural analyzes, two conserved clusters of hydrophobic residues in interactions have been identified in lipocalins. Since the residues implicated are not conserved for function, they should provide the minimal subset necessary to confer the lipocalin fold. This information has been used to assign LIR2 to lipocalins and to investigate its structure/function relationship. This study could be applied to other protein families with low pairwise similarity, such as the structurally related fatty acid binding proteins or avidins.

Project description:We present a fragment-search based method for predicting loop conformations in protein models. A hierarchical and multidimensional database has been set up that currently classifies 105,950 loop fragments and loop flanking secondary structures. Besides the length of the loops and types of bracing secondary structures the database is organized along four internal coordinates, a distance and three types of angles characterizing the geometry of stem regions. Candidate fragments are selected from this library by matching the length, the types of bracing secondary structures of the query and satisfying the geometrical restraints of the stems and subsequently inserted in the query protein framework where their fit is assessed by the root mean square deviation (r.m.s.d.) of stem regions and by the number of rigid body clashes with the environment. In the final step remaining candidate loops are ranked by a Z-score that combines information on sequence similarity and fit of predicted and observed phi/psi main chain dihedral angle propensities. Confidence Z-score cut-offs were determined for each loop length that identify those predicted fragments that outperform a competitive ab initio method. A web server implements the method, regularly updates the fragment library and performs prediction. Predicted segments are returned, or optionally, these can be completed with side chain reconstruction and subsequently annealed in the environment of the query protein by conjugate gradient minimization. The prediction method was tested on artificially prepared search datasets where all trivial sequence similarities on the SCOP superfamily level were removed. Under these conditions it is possible to predict loops of length 4, 8 and 12 with coverage of 98, 78 and 28% with at least of 0.22, 1.38 and 2.47 A of r.m.s.d. accuracy, respectively. In a head-to-head comparison on loops extracted from freshly deposited new protein folds the current method outperformed in a approximately 5:1 ratio an earlier developed database search method.

Dataset Information

Alignment of distantly related protein structures: algorithm, bound and implications to homology modeling.

Publications

Alignment of distantly related protein structures: algorithm, bound and implications to homology modeling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets