In-silico TAT-PTD prediction for cell penetrating peptides

Cell Penetrating Peptides (CPP) enhance transport of membrane and secretory proteins across hydrophobic membranes. Natural or synthetic CPP water soluble peptides translocate across cell membranes and are used for intracellular delivery of large hydrophilic molecules. HIV-TAT PTD with an amino acid sequence of YGRKKRRQRRR is the core of TAT protein in HIV, with 8 of its 11 TAT-PTD amino acids being hydrophilic yet this molecule diffuses readily through hydrophobic bi-lipid membranes. The effect of charged amino-acids in TAT-PTD on membrane transport was therefore evaluated In silico. A dataset of 168 sequences was created mutating the original TAT-PTD 11-amino acid sequence. Qikprop was used to predict ADME properties and a correlation of R2 = 73.7% between partition coefficient and skin permeability was found.