Peptide inhibitors were designed to have improved in situ binding compared to naturally occurring sequences using the residuespecific all-atom probability discriminatory function (RAPDF) [24] . The x-ray diffraction structure of DENV-2 envelope protein (Protein Data Bank identifier 1OAN) was used as a template for creating mutant structures from which the peptides were derived [14] . For each peptide, we randomly selected a residue side chain and substituted it with a new side chain. The substitution was performed using a backbone-dependent side chain rotamer library and a linear repulsive steric energy term provided by SCWRL version 3.0 [34] . The resulting all-atom models were energy minimized for 200 steps using the Energy Calculation and Dynamics (ENCAD) program [35] [36] [37] . RAPDF scores were then calculated to estimate the structural stability of a given E protein structure derivative. For a selected residue, side chain substitution was carried out ten times. The amino acid that produced the best RAPDF score was selected and used as a template for further mutation. The entire mutation process was repeated 100,000 times to enable a rigorous search for peptides that produced the best RAPDF score (i.e., highest predicted stability).