Fig. 3

Mutation hotspots that cause protease structures to be unstable when resisting PIs. The hotspots were detected based on vibrational entropy (ΔS) using ENCoM [41] for seven major mutation-containing protease-PI complexes: Atazanavir (ATV_1), Darunavir (DRV_1), Indinavir (IDV_1), Lopinavir (LPV_1), Nefinavir (NFV_1), Saquinavir (SQV_1), and Tipranavir (TPV_1). The major mutations that reduced the PI susceptibility are underlined. Common hotspots among PIs are highlighted in coloured boxes and ovals. The size of the residue columns is reciprocal to the total number of mutations in each complex. Heat maps are generated by the ENCoM