NOXclass: prediction of protein-protein interaction types
Definition of interface properties (paper)
In order to characterize the different types of protein-protein interactions, we analyzed the following six interface properties: interface area, ratio of interface area to protein surface area, amino acid composition of the interface, correlation between amino acid compositions of interface and protein surface, gap volume index, and conservation score of the interface. A residue is defined as being part of the interface if its solvent accessible surface area (SASA) decreases by > 1 Å2 upon the formation of the complex [13]. A protein-protein interface is defined to be the ensemble of all interface residues from both protomers. Solvent accessible surface areas for residues were calculated using NACCESS [35], with a probe sphere of radius 1.4 Å.
Interface area
Interface
area is defined as one half of the total decrease of SASA (ΔSASA) of
the two protomers upon the formation of the interaction:
where a and b are two protomers in the complex ab; SASAa, SASAb and SASAab are the SASA values for a, b, and ab, respectively. The native complex may contain additional protomers, but they are not considered.
Interface area ratio
Biological
interactions that involve a small protomer cannot have large interface
areas. This applies to some enzyme-inhibitor complexes, for instance.
Therefore, we defined a new feature, in which the interface area is
normalized by the SASA of the smaller protomer in the complex:
where SASAa and SASAb are the SASA values for protomers a and b, respectively.
Amino acid composition of the interface
We calculated both number-based and area-based amino acid composition [9]. The number-based amino acid composition (vn)
is defined as the frequency of each type of the 20 standard amino acids
in the protein-protein interface. By weighting each residue with its
ΔSASA, the area-based amino acid composition va is computed:
where type(r) is the type of the amino acid of residue r.
The Δν distance between two vectors ν and ν' of amino acid composition, number or area-based, is defined as [9,14]:
Interface Properties (web)
To discriminate the three types of interactions, we utilize the following interface properties.- interface
area
Interface area is defined as one half of the total decrease of solvent accessible surface area (SASA) of the two protomers upon the formation of the interaction. NACCESS [2] has been used to calculate the SASA for proteins.
- interface area ratio
Biological interactions in which a small protomer is involved, cannot have large interface areas. This applies to some enzyme-inhibitor complexes, for instance. Therefore, we defined a new feature, interface area ratio, in which the interface area is normalized by the SASA of the smaller protomer in the complex.
- area-based amino acid
composition of protein-protein interface
To calculate area-based amino acid composition for protein-protein interface, we first obtain number-based amino acid composition, which is defined as the frequency of each type of the 20 standard amino acids in the protein-protein interface. The area-based amino acid composition is then computed by weighting each residue with its decrease of SASA upon the formation of the interaction.
- correlation between
area-based amino acid compositions of interface and the rest of protein
surface
The amino acid composition of the biological interface was shown to be significantly different from that of the rest of the protein surface [3]. It is reasonable to expect the amino acid composition of the crystal packing interface to be similar to that of the rest of the protein surface. To measure this effect, the Pearson's correlation coefficient between the amino acid compositions of interface and surface were calculated. These correlations were calculated for both number-based and area-based amino acid compositions.
- gap volume index
Gap volume between two protomers is calculated using SURFNET [4]. The gap volume value is then normalized using interface area to produce a gap volume index [5].
- conservation score of
protein-protein interface
We calculated the conservation scores for residues in the interface as determined by the ConSurf method [6]. In a similar way to the area-based amino acid composition, we weighted the conservation score for each residue by its decrease of SASA upon the formation of the interaction. The average of these weighted residue conservation scores was used as the area-based conservation score of the interface.
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