Title:
Ab initio modeling of small proteins by iterative TASSER simulations
Ab initio modeling of small proteins by iterative TASSER simulations
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Author(s)
Wu, Sitao
Skolnick, Jeffrey
Zhang, Yang
Skolnick, Jeffrey
Zhang, Yang
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Abstract
Background: Predicting 3-dimensional protein structures from amino-acid sequences is an
important unsolved problem in computational structural biology. The problem becomes relatively
easier if close homologous proteins have been solved, as high-resolution models can be built by
aligning target sequences to the solved homologous structures. However, for sequences without
similar folds in the Protein Data Bank (PDB) library, the models have to be predicted from scratch.
Progress in the ab initio structure modeling is slow. The aim of this study was to extend the TASSER
(threading/assembly/refinement) method for the ab initio modeling and examine systemically its
ability to fold small single-domain proteins.
Results: We developed I-TASSER by iteratively implementing the TASSER method, which is used
in the folding test of three benchmarks of small proteins. First, data on 16 small proteins (< 90
residues) were used to generate I-TASSER models, which had an average Cα-root mean square
deviation (RMSD) of 3.8Å, with 6 of them having a Cα-RMSD < 2.5Å. The overall result was
comparable with the all-atomic ROSETTA simulation, but the central processing unit (CPU) time
by I-TASSER was much shorter (150 CPU days vs. 5 CPU hours). Second, data on 20 small proteins
(< 120 residues) were used. I-TASSER folded four of them with a Cα-RMSD < 2.5Å. The average
Cα-RMSD of the I-TASSER models was 3.9Å, whereas it was 5.9Å using TOUCHSTONE-II
software. Finally, 20 non-homologous small proteins (< 120 residues) were taken from the PDB
library. An average Cα-RMSD of 3.9Å was obtained for the third benchmark, with seven cases
having a Cα-RMSD < 2.5Å.
Conclusion: Our simulation results show that I-TASSER can consistently predict the correct folds
and sometimes high-resolution models for small single-domain proteins. Compared with other ab
initio modeling methods such as ROSETTA and TOUCHSTONE II, the average performance of ITASSER
is either much better or is similar within a lower computational time. These data, together
with the significant performance of automated I-TASSER server (the Zhang-Server) in the 'free
modeling' section of the recent Critical Assessment of Structure Prediction (CASP)7 experiment,
demonstrate new progresses in automated ab initio model generation. The I-TASSER server is
freely available for academic users http://zhang.bioinformatics.ku.edu/I-TASSER.
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Date Issued
2007-05-08
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