Residue depth (RD) is a
solvent exposure measure that describes to what extent a
residue is buried in the
protein structure
Protein structure is the three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers specifically polypeptides formed from sequences of amino acids, the monomers of the polymer. A single amino acid monomer ma ...
space. It complements the information provided by conventional
accessible surface area
The accessible surface area (ASA) or solvent-accessible surface area (SASA) is the surface area of a biomolecule that is accessible to a solvent. Measurement of ASA is usually described in units of square angstroms (a standard unit of measureme ...
(ASA).
Currently, predictions in regards to whether a residue is exposed or buried are used in a wide variety of protein structure prediction engines. Such prediction can provide valuable information for
protein fold
A protein superfamily is the largest grouping (clade) of proteins for which common ancestry can be inferred (see homology). Usually this common ancestry is inferred from structural alignment and mechanistic similarity, even if no sequence simila ...
recognition,
functional residue prediction and protein
drug design
Drug design, often referred to as rational drug design or simply rational design, is the invention, inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic compound, organi ...
. Several biophysical properties of proteins have been shown to correlate with residue depth, including mutant protein stability, protein-protein interface hot-spot, H/D exchange rate of residue and residue conservation.
Residue depth has also been utilized in predicting small molecule binding site on proteins, with accuracy statistically on par with other conventional methods. The method has the advantageous of being simple and intuitive. The method has been reported to detect unconventional flat binding sites.
To date several approaches have been proposed to predict RD values from
protein sequence
Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthesi ...
s. Yuan and Wang proposed a computational framework that uses sequential evolutionary information contained in
PSI-BLAST
In bioinformatics, BLAST (basic local alignment search tool) is an algorithm and program for comparing primary biological sequence information, such as the amino-acid sequences of proteins or the nucleotides of DNA and/or RNA sequences. A B ...
profiles and the global protein size information to quantify the relationship between RD and protein sequence. Zhang et al. proposed the RDpred method to predict RD values based on predicted
secondary structure
Protein secondary structure is the three dimensional form of ''local segments'' of proteins. The two most common secondary structural elements are alpha helices and beta sheets, though beta turns and omega loops occur as well. Secondary structur ...
, residue position and PSI-BLAST profile. More recently, Song et al. described another sequence-based method that also uses support vector regression to quantify the RD-sequence relationship. Their webserver Prodepth, is developed to facilitate RD prediction analysis for sequences submitted by interested users. In addition, Prodepth server can predict the solvent-accessible surface area (ASA) value for each residue for users' submitted sequence. Based on the predicted ASA and RD values, it will further output the two-state solvent accessibility prediction by classifying a residue as being exposed or buried.
Currently, residue depth has been used for several applications. One of these is predicting the pKa of an ionizable group.
The pKa equation is a linear combination of a few features, including: depth, number of hydrogen bond, electrostatic energy, solvent accessible surface area. Among these features, depth has a major contribution.
References
External links
DEPTH web server— Protein depth computation and small molecule binding site prediction. Free source downloads
Prodepth server— Protein depth and accessible surface area prediction using sequence information
{{DEFAULTSORT:Residue Depth
Amino acids
Protein structure