Disclosed are peptides that exhibit good binding to the anticodon stem and loop of human lysine tRNA species, tRNALys3. The starting point was the 15-amino-acid sequence, RVTHHAFLGAHRTVG, found to bind selectively to hypermodified tRNALys3. The peptide backbone conformation was determined via atomistic simulation of the peptide-ASLLys3complex and then held fixed throughout the search. Analysis of the binding structure and the various contributions to the binding energy shows that: 1) two hydrophilic residues (asparagine (ASN) at site 11 and the cysteine (CYS) at site 12) “recognize” the ASLLys3 due to the VDW energy, and thereby contribute to its binding specificity, and 2) the positively-charged arginines (ARG) at sites 4 and 13 preferentially attract the negatively-charged sugar rings and the phosphate linkages, and thereby contribute to the binding affinity.
