To identify additional novel peptide inhibitors and their corresponding targets, a 20 residue sliding window that moved from the N to the C terminus of the DENV-2 strain S1 E protein (PDB ID 1OAN) in 10 residue acid increments was evaluated by a structural stability (pseudoenergy) optimization protocol using the RAPDF. A Metropolis Monte Carlo search algorithm [38] was used to change each amino acid in the 20 residue window to one of the 19 other naturally occurring amino acids, and the stability of each corresponding peptide in the context of the entire E protein structure was evaluated. Our approach identified four E protein regions with the potential for the highest in situ binding affinities. These correspond to DENV-2 strain S1 E protein amino acids 41-60, 131-150, 251-270, and 351-370 (see Figure 1 ) that were selected for synthesis and antiviral testing (1OAN1, 1OAN2, 1OAN3, and 1OAN4).