Dataset Information

Interplay of I-TASSER and QUARK for template-based and ab initio protein structure prediction in CASP10.

ABSTRACT: We develop and test a new pipeline in CASP10 to predict protein structures based on an interplay of I-TASSER and QUARK for both free-modeling (FM) and template-based modeling (TBM) targets. The most noteworthy observation is that sorting through the threading template pool using the QUARK-based ab initio models as probes allows the detection of distant-homology templates which might be ignored by the traditional sequence profile-based threading alignment algorithms. Further template assembly refinement by I-TASSER resulted in successful folding of two medium-sized FM targets with >150 residues. For TBM, the multiple threading alignments from LOMETS are, for the first time, incorporated into the ab initio QUARK simulations, which were further refined by I-TASSER assembly refinement. Compared with the traditional threading assembly refinement procedures, the inclusion of the threading-constrained ab initio folding models can consistently improve the quality of the full-length models as assessed by the GDT-HA and hydrogen-bonding scores. Despite the success, significant challenges still exist in domain boundary prediction and consistent folding of medium-size proteins (especially beta-proteins) for nonhomologous targets. Further developments of sensitive fold-recognition and ab initio folding methods are critical for solving these problems.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC4067246 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Interplay of I-TASSER and QUARK for template-based and ab initio protein structure prediction in CASP10.

Zhang Yang Y

Proteins 20130831

We develop and test a new pipeline in CASP10 to predict protein structures based on an interplay of I-TASSER and QUARK for both free-modeling (FM) and template-based modeling (TBM) targets. The most noteworthy observation is that sorting through the threading template pool using the QUARK-based ab initio models as probes allows the detection of distant-homology templates which might be ignored by the traditional sequence profile-based threading alignment algorithms. Further template assembly ref ...[more]

PMID: 23760925

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Project description:BackgroundPredicting 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.ResultsWe 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 Calpha-root mean square deviation (RMSD) of 3.8A, with 6 of them having a Calpha-RMSD < 2.5A. 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 Calpha-RMSD < 2.5A. The average Calpha-RMSD of the I-TASSER models was 3.9A, whereas it was 5.9A using TOUCHSTONE-II software. Finally, 20 non-homologous small proteins (< 120 residues) were taken from the PDB library. An average Calpha-RMSD of 3.9A was obtained for the third benchmark, with seven cases having a Calpha-RMSD < 2.5A.ConclusionOur 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 I-TASSER 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.

Project description:We have developed a new combined approach for ab initio protein structure prediction. The protein conformation is described as a lattice chain connecting C(alpha) atoms, with attached C(beta) atoms and side-chain centers of mass. The model force field includes various short-range and long-range knowledge-based potentials derived from a statistical analysis of the regularities of protein structures. The combination of these energy terms is optimized through the maximization of correlation for 30 x 60,000 decoys between the root mean square deviation (RMSD) to native and energies, as well as the energy gap between native and the decoy ensemble. To accelerate the conformational search, a newly developed parallel hyperbolic sampling algorithm with a composite movement set is used in the Monte Carlo simulation processes. We exploit this strategy to successfully fold 41/100 small proteins (36 approximately 120 residues) with predicted structures having a RMSD from native below 6.5 A in the top five cluster centroids. To fold larger-size proteins as well as to improve the folding yield of small proteins, we incorporate into the basic force field side-chain contact predictions from our threading program PROSPECTOR where homologous proteins were excluded from the data base. With these threading-based restraints, the program can fold 83/125 test proteins (36 approximately 174 residues) with structures having a RMSD to native below 6.5 A in the top five cluster centroids. This shows the significant improvement of folding by using predicted tertiary restraints, especially when the accuracy of side-chain contact prediction is >20%. For native fold selection, we introduce quantities dependent on the cluster density and the combination of energy and free energy, which show a higher discriminative power to select the native structure than the previously used cluster energy or cluster size, and which can be used in native structure identification in blind simulations. These procedures are readily automated and are being implemented on a genomic scale.

Dataset Information

Interplay of I-TASSER and QUARK for template-based and ab initio protein structure prediction in CASP10.

Publications

Interplay of I-TASSER and QUARK for template-based and ab initio protein structure prediction in CASP10.

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