Direct-coupling based contact prediction methods (DCA) enable de-novo
structure prediction of proteins with an unprecedented accuracy.
However, these methods require thousands of protein sequences to
achieve high accuracy, limiting their usability. Here, we introduce
PconsC3, a method to accurately predict contacts for families an
order of magnitude smaller than feasible with DCA, thus increasing
accurate contact predictions from 12% to 54% of all protein domain
families with unknown structure. Input features comprise contact
predictions by plmDCA, GaussDCA as well as PhyCMAP, secondary
structure prediction by PSIPRED 3.0, and solvent accessibility
prediction by NetSurfP 1.1. In PconsC3 PhyCMAP can be replaced by
another contact predictor and we have successfully used CMapPro with
similar accuracy. Additionally, CD-HIT is run to generate statistics
about the alignment (i.e. alignment depth at different sequence
similarity cut-offs). The initial layer of PconsC3 takes these
features as input and uses a random forest to predict a score for
each possible contact. On contrary to previous work, PconsC3 applies
pattern recognition already in the first layer. This results in an
intermediate contact map. Every following layer uses all the initial
features plus the output from the previous layer, given as a window
of 11 by 11 residues around the current contact.
This work used the
EGI infrastructure
with the support of IN2P3-IRES, INFN-CLOUD-BARI and TR-FC1-ULAKBIM.
Fig. 1: Workflow of PconsC3.
2. Usage
Input to the server is one or several (upto five) amino acid sequence(s) in FASTA format. The user can either paste
sequences in the text-area provided, or, alternatively,
upload a file containing your sequences.
Example input:
>1qj8A
ATSTVTGGYAQSDAQGQMNKMGGFNLKYRYEEDNSPLGVIGSFTYTEKSRTASSGDYNKN
QYYGITAGPAYRINDWASIYGVVGVGYGKFQTTEYPTYKNDTSDYGFSYGAGLQFNPMEN
VALDFSYEQSRIRSVDVGTWIAGVGYRF
3. Output
The server outputs the contact predictions using PconsC3
method in plain text format. The predicted contacts are also
displayed graphically. Additionally, a zipped folder including the
input sequence, predicted contacts (plain text and graphical
representation) and multiple sequence alignments is also downloadable.
4. References
Skwark MJ, Michel M, Hurtado DM, Ekeberg M, Elofsson A. "Accurate contact predictions for thousands of protein families using PconsC3."
Skwark MJ, Raimondi D, Michel M, Elofsson A (2014) "Improved Contact Predictions Using the Recognition of Protein Like Contact Patterns." PLoS Computational Biology 10(11).
