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A template‐finding algorithm and a comprehensive benchmark for homology modeling of proteins
Author(s) -
Vallat Brinda Kizhakke,
Pillardy Jaroslaw,
Elber Ron
Publication year - 2008
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21976
Subject(s) - template , threading (protein sequence) , modeller , protein data bank (rcsb pdb) , computer science , homology modeling , casp , protein structure prediction , structural alignment , algorithm , protein data bank , homology (biology) , tree (set theory) , benchmark (surveying) , decision tree , structural bioinformatics , protein structure , artificial intelligence , sequence alignment , mathematics , peptide sequence , programming language , combinatorics , biology , gene , biochemistry , enzyme , geodesy , geography
The first step in homology modeling is to identify a template protein for the target sequence. The template structure is used in later phases of the calculation to construct an atomically detailed model for the target. We have built from the Protein Data Bank (PDB) a large‐scale learning set that includes tens of millions of pair matches that can be either a true template or a false one. Discriminatory learning (learning from positive and negative examples) is used to train a decision tree. Each branch of the tree is a mathematical programming model. The decision tree is tested on an independent set from PDB entries and on the sequences of CASP7. It provides significant enrichment of true templates (between 50 and 100%) when compared to PSI‐BLAST. The model is further verified by building atomically detailed structures for each of the tentative true templates with modeller. The probability that a true match does not yield an acceptable structural model (within 6 Å RMSD from the native structure) decays linearly as a function of the TM structural‐alignment score. Proteins 2008. © 2008 Wiley‐Liss, Inc.