List of protein structure prediction software

This list of protein structure prediction software summarizes commonly used software tools in protein structure prediction, including homology modeling, protein threading, ab initio methods, secondary structure prediction, and transmembrane helix and signal peptide prediction.

Software highlight

Main article: Protein structure prediction

I-TASSER is the best server for protein structure prediction according to the 2006-2012 CASP experiments (CASP7, CASP8, CASP9 and CASP10). The standalone I-TASSER package is freely available for download.

HHpred was the leading server for template-based protein structure prediction in the 2010 CASP9 experiment. It has a median response time of a few minutes instead of days like other top-performing servers. HHpred is often used for remote homology detection and homology-based function prediction. It runs with the free, open-source software package HH-suite for fast sequence searching, protein threading and remote homology detection.

RaptorX excels at aligning hard targets according to the 2010 CASP9 experiments. RaptorX generates the significantly better alignments for the hardest 50 CASP9 template-based modeling targets than other servers including those using consensus and refinement methods. The RaptorX server is available at server

MODELLER is a popular software tool for producing homology models by satisfaction of spatial restraints using methodology derived from NMR spectroscopy data processing. The ModWeb comparative protein structure modeling web-server uses primarily MODELLER for automatic comparative modeling.

SWISS-MODEL provides an automated web server for protein structure homology modeling.

bioinfo.pl and Robetta widely used servers for protein structure prediction.

SPARKSx is one of the top performing servers in the CASP focused on the remote fold recognition.

PEP-FOLD is a de novo approach aimed at predicting peptide structures from amino acid sequences, based on a HMM structural alphabet.

Phyre and Phyre2 are amongst the top performing servers in the CASP international blind trials of structure prediction in homology modelling and remote fold recognition, and are designed with an emphasis on ease of use for non-experts.

RAPTOR (software) is a protein threading software that is based on integer programming. The basic algorithm for threading is described in Bowie (1991) and is fairly straightforward to implement.

QUARK is an algorithm developed for ab initio protein structure modeling.

Abalone is a Molecular Dynamics program for folding simulations with explicit or implicit water models.

TIP is a knowledgebase of STRUCTFAST models and precomputed similarity relationships between sequences, structures, and binding sites. Several distributed computing projects concerning protein structure prediction have also been implemented, such as the Folding@home, Rosetta@home, Human Proteome Folding Project, Predictor@home, and TANPAKU.

Princeton_TIGRESS (server) is a protein structure refinement server whose underlying method was ranked in 5th place in blind predictions during CASP10 <http://predictioncenter.org/casp10/doc/presentations/ranking_CASP10_refinement_DJ.pdf>. It uses monte carlo and molecular dynamics based sampling techniques and support vector machines for selection. It can consistently increase the model accuracy of many top 3-D structure prediction servers' predictions, increasing the potential usability of a predicted structure in a biological application.

CABS-FOLD is a server that provides tools for protein structure prediction from sequence only (de novo modeling) and also using alternative templates (consensus modeling).

Bhageerath is another Ab-initio modelling server.

The Foldit program seeks to investigate the pattern-recognition and puzzle-solving abilities inherent to the human mind in order to create more successful computer protein structure prediction software.

BBSP (Building Blocks Structure Predictor) is a program that makes use of Hybrid template-based approaches, which associate fragment conformations for the sequence and detect distant fold similarities based on the fragment similarities <http://rsif.royalsocietypublishing.org/content/11/95/20131147>. Also, such program is assisted by a secondary structure prediction algorithm named HCAM, which is mainly based on hydropathy profile analysis and is included in the BBSP tools suite.

Computational approaches provide a fast alternative route to antibody structure prediction. Recently developed antibody F_V region high resolution structure prediction algorithms, like RosettaAntibody, have been shown to generate high resolution homology models which have been used for successful docking.

Homology modeling

Main article: Homology modeling

Name	Method	Description	Link
3D-JIGSAW	Fragment assembly	Automated webserver	server
RaptorX	remote homology detection, protein 3D modeling, binding site prediction	Automated webserver and Downloadable program	server and download
Biskit	wraps external programs into automated workflow	BLAST search, T-Coffee alignment, and MODELLER construction	project site
CABS	Reduced modeling tool	Downloadable program	download
CPHModel	Fragment assembly	Automated webserver	server
EasyModeller	GUI to MODELLER	Standalone windows executable	download
ESyPred3D	Template detection, alignment, 3D modeling	Automated webserver	server
FoldX	Energy calculations and protein design	Downloadable program	download
GeneSilico	Consensus template search/fragment assembly	Webserver	server
Geno3D	Satisfaction of spatial restraints	Automated webserver	server
HHpred	Template detection, alignment, 3D modeling	Interactive webserver with help facility	server download article
LIBRA I	LIght Balance for Remote Analogous proteins, ver. I	Webserver	server
LOMETS	Local Meta threading server	Meta-server combining 9 different programs	Server download
MODELLER	Satisfaction of spatial restraints	Standalone program mainly in Fortran and Python	download Server
Phyre and Phyre2	Remote template detection, alignment, 3D modeling, multi-templates, ab initio	Webserver with job manager, automatically updated fold library, genome searching and other facilities	server
Prime	Physics-based energy function	Graphical interface, sequence alignment, secondary structure prediction, homology modeling, protein refinement, loop-prediction, and side-chain prediction	Download
Protinfo CM	Comparative modelling of protein structure using minimum perturbation and loop building	Web server	server
ROBETTA	Rosetta homology modeling and ab initio fragment assembly with Ginzu domain prediction	Webserver	server
BHAGEERATH-H	Combination of ab initio folding and homology methods	Protein tertiary structure predictions	server
Selvita Protein Modeling Platform	Package of tools for protein modeling	Free demo, interactive webserver and standalone program including: BLAST search, CABS modeling, 3D threading, Psi-Pred secondary structure prediction	Home page
STRUCTUROPEDIA	WebInterface to MODELLER	Homology modeling of proteins in monomeric or multimeric forms alone and in complex with peptides and DNA as well as introduction of mutations and post-translational modifications (PTMs) into protein structures	server
SWISS-MODEL	Local similarity/fragment assembly	Automated webserver (based on ProModII)	server
TIP-STRUCTFAST	Automated Comparative Modeling	Webserver and knowledgebase	server
WHAT IF	Position specific rotamers	Standalone program and webinterface	Home page Webinterface
Yasara	Detection of templates, alignment, modeling incl. ligands and oligomers, hybridization of model fragments	Graphical interface or text mode (clusters)	Home page CASP8 results

Threading/fold recognition

Main article: Protein threading

Name	Method	Description	Link
RaptorX	Remote template detection, single-template and multi-template threading, totally different from and much better than the old program RAPTOR designed by the same group	Webserver with job manager, automatically updated fold library	download server
3D-PSSM	3D-1D sequence profiling (replaced by Phyre)	Webserver	server
Bioingbu	Evolutionary information recognition	Webserver	server
HHpred	Template detection, alignment, 3D modeling	Interactive webserver with help facility	server download article
NovaFold	Combination of threading and ab initio folding	Commercial protein structure prediction application	Home page
I-TASSER	Combination of ab initio folding and threading methods	Structural and function predictions	server download
LOOPP	Multiple methods	Webserver	server
mGenTHREADER/GenTHREADER	Sequence profile and predicted secondary structure	Webserver	main page
MUSTER	profile-profile alignment	Webserver	server download
Phyre and Phyre2	Remote template detection, alignment, 3D modeling, multi-templates, ab initio	Webserver with job manager, automatically updated fold library, genome searching and other facilities	server
RAPTOR	Integer programming based fold recognition	Free demo	download articles
Selvita Protein Modeling Platform	Package of tools for protein modeling	Free demo, interactive webserver and standalone program including: 3D threading and flexible 3d threading	Home page
SUPERFAMILY	Hidden Markov modeling	Webserver/standalone	main page
SPARKS-X	3D structure modeling by Fold recognition according to Sequence profiles and structural profiles	Webserver	Server
BBSP - Building Blocks Structure Predictor	Hybrid template-based	Free application plus database	main page

Ab initio structure prediction

Main article: De novo protein structure prediction

Name	Method	Description	Link
EVfold	Evolutionary couplings calculated from correlated mutations in a protein family, used to predict 3D structure from sequences alone and to predict functional residues from coupling strengths. Predicts both globular and transmembrane proteins.	Webserver	Server
QUARK	Monte Carlo fragment assembly	On-line server for protein modeling (best for ab initio folding in CASP9)	Server
NovaFold	Combination of threading and ab initio folding	Commercial protein structure prediction application	Home page
I-TASSER	Threading fragment structure reassembly	On-line server for protein modeling	Server download
Selvita Protein Modeling Platform	Package of tools for protein modeling	Interactive webserver and standalone program including: CABS ab initio modeling	Home page
ROBETTA	Rosetta homology modeling and ab initio fragment assembly with Ginzu domain prediction	Webserver	server
Rosetta@home	Distributed-computing implementation of Rosetta algorithm	Downloadable program	main page
CABS	Reduced modeling tool	Downloadable program	download
CABS-FOLD	Server for de novo modeling, can also use alternative templates (consensus modeling).	Webserver	server
Bhageerath	A computational protocol for modeling and predicting protein structures at the atomic level.	Webserver	Server
Abalone	Molecular Dynamics folding	Program	Example
PEP-FOLD	De novo approach, based on a HMM structural alphabet	On-line server for peptide structure prediction	Server

Secondary structure prediction

Main article: Protein structure prediction § Secondary_structure

Detailed list of programs can be found at List of protein secondary structure prediction programs

Transmembrane helix prediction

Main article: Transmembrane helix prediction

Name	Method	Description	Link
HMMTOP	Hidden Markov Model	Webserver/standalone	main page
MEMSAT	Neural networks and SVMs	Webserver/standalone	main page
PHDhtm in PredictProtein	Multiple alignment-based neural network system	Webserver/standalone	server
Phobius	Homology supported predictions	Webserver/standalone	main page
TMHMM	Hidden Markov Model	Webserver/standalone	main page
SVMTop2	Support Vector Machines	Webserver	main page

Signal peptide prediction

Name	Method	Description	Link
SignalP	artificial neural networks and hidden Markov models	Webserver/standalone	server

See also

• List of protein secondary structure prediction programs
• List of nucleic acid simulation software
• List of software for molecular mechanics modeling
• Molecular design software
• Protein design