Biomedical Engineering Reference
In-Depth Information
pairs, of which 2,719 for enzymes, 1,372 for ion channels, 630 for GPCRs, and 82
for nuclear receptors. The negative datasets were derived with the following steps
(1) separated the pairs in the above positive dataset into single drugs and proteins,
(2) recoupled these singles into pairs in a way that none of them occurs in the
corresponding positive dataset, and (3) randomly picked the negative pairs thus
formed until they reached the number two times as many as the positive pairs. The
representative targets have been classified into 28 common groups based on their
functional groups. A nearest neighbor algorithm has been used to identify the
drug-target interaction pairs using different amino acid properties such as
hydrophobicity, polarizability, polarity, secondary structure, normalized van der
Waals volume, and solvent accessibility. This method showed a cross-validation
accuracy of 85, 81, 78, and 86% for the drug target pairs with enzymes, ion
channels, GPCRs, and nuclear receptors, respectively.
Huang et al. [
94
] developed a dataset of 1,268 approved human target proteins
stored in DrugBank database and 7,252 nondrug targets. Among the dataset 31 and
16 ion channels were identified as ion channel target and ion-channel nontarget
proteins. They utilized different properties of amino acid residues such as compo-
sition, hydrophobicity, polarity, polarizability and normalized van der Waals vol-
ume and RBF networks for discriminating the drug and nondrug targets. They
showed that the drug and nondrug targets for the whole dataset can be discriminated
with an accuracy of 85% and for the ion channel proteins with an accuracy of 84%.
6 Conclusions
This review is focused on the development of databases and prediction methods for
understanding the structure and function of membrane proteins. The methods
proposed for identifying transmembrane helical proteins and predicting their mem-
brane spanning segments have been reviewed. The transmembrane helical proteins
have a continuous stretch of hydrophobic residues in their membrane spanning
segments, whereas membrane spanning
-barrel membrane
proteins have both polar and charged residues along with hydrophobic residues.
The advances made for detecting such type of proteins in genomic sequences and
predicting their membrane spanning
b
-strand segments in
b
-strand segments have been discussed. On the
functional front, the databases developed for transporters, ion channels and func-
tionally important residues in membrane proteins have been outlined. Further, the
discrimination methods for identifying membrane transporters and predicting
transporters into three classes and six families have been described. In addition,
recent methods for predicting the subclasses of ion channels as well as ion-
channels-drug interactions have been explained. In essence, this comprehensive
review provides the insights into understanding the structure and functions of
membrane proteins along with ion channel proteins.
b
