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FATCAT - Help Page


OVERVIEW

The FATCAT server provides access to a flexible protein structure alignment algorithm. In flexible alignment, rotations and translations between elements of one structure are allowed to minimize the overall root mean square deviation (RMSD) between the compared structures. This makes it possible to effectively align and compare protein structures even if they underwent structural rearrangements in different functional forms, different crystallization conditions or as a result of mutations. The server uses contact and distance maps, a morphing algorithm and other graphical presentations to visualize the differences between two protein conformations in an intuitive way.

FATCAT excutables for Linux x84_64 can be downloaded here

PAIRWISE ALIGNMENT

Comparison of two protein structures using FATCAT algorithm. Structures can be uploaded or retrieved from the PDB or SCOP database by entering their accession codes. FATCAT then calculates their structural alignment using the rigid or flexible option.
See a sample report

Search for structures with structural similarity to the query structure. Users can upload a structure file in PDB format or input the PDB or SCOP accession as the query. SCOP and PDB databases clustered at 90% and 40% sequence identity are available for searches. Search can be performed with the rigid or flexible option of the FATCAT algorithm. NOTE: Fatcat search by structural similarity is time consuming - calculations may take several hours or longer depending on the size of the structure.

See a sample report

Search for structures with sequence similarity the query. Users can upload a structure file in the PDB format or input the PDB or SCOP accession code as the query. Blast is then used to collect structures with sequences similar to the sequence of the query (with sequence identity cutoff of 60%) and, subsequently, FATCAT is used to compare these structures to the query structure. Sequences of structures from the full PDB database are available for searches.
See a sample report

GLOSSARY OF TERMS

AFP (Aligned Fragment Pair)
Given two protein structures, an AFP is defined as a match of two fragments, one from each structure. Each AFP defines the transformation (rotation and translation) needed to superimpose the fragments included in it. The figure below shows two AFPs, which define two different transformations of the input structures.


Twist
As shown in the schematic example below, the green structure has to be rearranged by introducing a twist at the hinge (pointed to by the arrow) so that the green and red structures can be better aligned (i.e., including 1-4 AFPs, instead of only two, either 1-2 or 3-4).


FATCAT (chaining) score
In FATCAT, flexible structure alignment is formulated as an AFP chaining process (the path connected by blue dotted lines in the example alignment graph below) allowing at most t twists (here t=5). Dynamic programming is used in the chaining process (as shown in the figure below). If we denote S(k) as the best score of paths ending at the AFP k, then it can be calculated from the best score of paths ending at previous AFPs that can be connected to the k-th AFP, subject to the constraints.

where a(k) is the score of AFP k itself, determined by its RMSD and length with long AFPs rewarded and large RMSDs penalized; is the score of introducing a connection between AFP m and AFP k, defined by a function of the compatibility of the AFPs and the mis-matched regions and/or gaps created by the connection of the two AFPs; T(k) is the number of twists required to connect the chain of AFPs leading up to S(k).

The FATCAT (chaining) score is the best of all S(k) in the alignment graph.

P-value
A P-value is used in FATCAT to evaluate the significance of the detected structural similarities detected. It is the probability of observing a similarity score higher than the one currently obtained, for unrelated structures. It is calculated based on the observation that the FATCAT similarity score between two unrelated structures follows the extreme value distribution. The FATCAT similarity score incorporates the FATCAT chaining score, the RMSD of the resulting superposition, the number of equivalent positions in the alignment and the number of twists.

The FATCAT similarity score is computed as

where cs is the FATCAT chaining score; L is the number of equivalent positions in the alignment; RMSD is the overall RMSD between two the structures when one structure is rearranged at the positions where twists are detected by FATCAT; N is the number of blocks in the alignment (number of twists + 1).

The p-value of s is then computed as

where the location and the scale parameter of the extreme value distribution of FATCAT similarity scores of unrelated structures were determined by empirical simulation. For more details about FATCAT significance calculation and examples illustrating its possible biological interpretations, please see the original publication.

align-len

The length of the alignment (including gaps)

opt-len

The number of equivalent positions in the alignment
opt-len = align-len - gaps

opt-rmsd

The root mean square deviation (RMSD) of aligned Cα atoms of the input structures, with one input structure rearranged if flexibility is detected (by introducing twists in the alignment).

chain-rmsd
The root mean square deviation (RMSD) of aligned Cα atoms of the input structures, without structural rearrangement (twists) even if structural flexibility is detected in the alignment. It means that in the cases with flexibility (when twists are introduced to get the alignment), the value of chain-rmsd could be very high (because flexible alignment is longer than rigid alignment would be). The comparison of chain-rmsd and opt-rmsd makes it possible to asses how signifcantly the introduced conformational flexibility improved the alignment.

transformed 'complete' structure
In FATCAT, only the Cα atoms of a single chain from two input structures are aligned. If users choose to download a "complete" structure, the server applies the transformation matrix to the "original" structure file (which may contain coordinates of other chains, ligands etc) and returns the transformed file. This output file is only available for FATCAT pairwise alignment calculated with the rigid option.
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Current support provided by NIH grant GM101457 - Development of the Flexible Comparative Modeling Toolkit, Previous supports provided by NSF grant DBI-0349600, NIH grant GM63208 and NIH grant GM076221