Tertiary Structure Tools


Sensitive protein homology detection and structure prediction by HMM-HMM-comparison. Starting from a query sequence, HHpred builds a multiple sequence alignment using HHblits and turns it into a profile HMM. This is then compared it with a database of HMMs representing proteins with known structure (e.g. PDB, SCOP) or annotated protein families (e.g. PFAM, SMART, CDD, COGs, KOGs). The output is a list of closest homologs with alignments. HHpred can also build 3D homology models using the identified templates in the PDB database. It can optimize template picking and query-template alignments for homology modeling.
The HHblits software is part of the open source package HHsuite.



bFit is a probabilistic method for robust superposition and comparison of protein structures. To do so, non-rigid displacements in protein structures are modelled with outlier-tolerant probability distributions.



Build a customized library of structural fragments, excised from PDB structures. The HHfragments are variable in length homologous, remotely homologous or analogous pieces of recurrent local structure, which can be readily used in ab initio protein structure prediction.



Program for Comparative Protein Structure Modelling by Satisfaction of Spatial Restraints.
[A. Sali and T.L. Blundell. Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol. 234, 779-815, 1993. http://salilab.org/modeller/]



SamCC measures local parameters of (a)symmetric, parallel, and antiparallel four-helical coiled-coils. Briefly, SamCC divides coiled-coil bundle into layers (slices), brings each layer into an idealized state (expected from equations), then performing final calculations on the resulting idealized structure.



PDBalert is a web-based automatic system that alerts users as soon as a pdb structure with homology to a protein of interest becomes available. Users can upload their personal protein sequences of interest. Once a week, when new proteins are released to the PDB database, PDBalert compares these with the users' sequences. When a significant match is found, the user is alerted by an email containing a link to the search results.


External tertiary structure prediction servers


FFAS was the first structure prediction server based on profile-profile comparison. This sensitive server has the advantage of being interactive and fast. Also, it allows scanning other databases like PFAM, PDB, SCOP and COG. In addition to database searches, pairwise alignment is possible.



I-TASSER was ranked best in tertiary structure prediction (as 'Zhang-Server') in the community-wide blind benchmarks CASP7 and CASP8. It uses mainly profile-profile comparison to identify templates and alignments for deriving distance constraints. Its power lies in how it combines the distance constraints from up to the 50 best-ranked templates. It performs some knowledge-based free modelling in regions without any template-based information.



The Genesilico metaserver sends requests to more than 10 autonomous servers and presents the individual results in an easily interpretable, uniform format. May take a few hours for complete results. Simple registration via e-mail required.



Robetta is a metaserver that relies on autonomous servers like FFAS when a significant match to a known structure can be found. When nothing significant is found, the Rosetta ab-initio structure prediction method from the same lab is employed to create a model. Best server for ab-initio prediction of protein structure (if everything else fails). Simple registration via browser required.


External tertiary structure analysis servers


Excellent server for the normal mode analysis of protein conformational movements. From a pdb file as input, the server calculates the lowest-energy normal modes. Very helpful animations for each mode are also provided. Relevance: In more than 50% of proteins with several known conformations, the movement between the two conformations corresponds to a combination of the lowest two normal modes. Normal modes may also improve MR in X-ray crystallography.