Abstract
Locating ligand binding sites and finding the functionally important residues from protein sequences as well as structures became one of the challenges in understanding their function. Hence a Naïve Bayes classifier has been trained to predict whether a given amino acid residue in membrane protein sequence is a ligand binding residue or not using only sequence based information. The input to the classifier consists of the features of the target residue and two sequence neighbors on each side of the target residue. The classifier is trained and evaluated on a nonredundant set of 42 sequences (chains with at least one transmembrane domain) from 31 alpha-helical membrane proteins. The classifier achieves an overall accuracy of 70.7% with 72.5% specificity and 61.1% sensitivity in identifying ligand binding residues from sequence. The classifier performs better when the sequence is encoded by psi-blast generated PSSM profiles. Assessment of the predictions in the context of three-dimensional structures of proteins reveals the effectiveness of this method in identifying ligand binding sites from sequence information. In 83.3% (35 out of 42) of the proteins, the classifier identifies the ligand binding sites by correctly recognizing more than half of the binding residues. This will be useful to protein engineers in exploiting potential residues for functional assessment.
Highlights
Membrane proteins are an important class of molecules which play key roles in various biologically important functions such as the maintenance of ionic and proton balance, transport of substrates, ions, energy, and information across the membrane, light harvesting, photosynthesis, and other biological processes [1]
The resulting dataset consists of 31 membrane proteins from which 42 sequences were considered in the present study with mutual sequence identity ≤ 30% using BLASTCLUST program from NCBI and each protein has at least 50 amino acid residues
We trained a Naıve Bayes classifier to predict whether a given amino acid residue in a membrane protein sequence is ligand binding or not based on its sequence information
Summary
Membrane proteins are an important class of molecules which play key roles in various biologically important functions such as the maintenance of ionic and proton balance, transport of substrates, ions, energy, and information across the membrane, light harvesting, photosynthesis, and other biological processes [1]. It has been estimated that nearly 45% of the drugs on the market target membrane protein receptors [2]. It has been estimated that, in many genomes, TM proteins comprise 20–35% of all proteins [3, 4] and significant progress has been made in recent years in the determination of the structures of membrane proteins. Attempts have been made to determine the complete structures or domains of membrane proteins by crystallographic and solution or solid-state NMR spectroscopy methods [5, 6]. This in turn increases the entries significantly in various structural databases
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