Electrooptical measurements on purple membrane containing the wild-type and 10 different bacteriorhodopsin mutants have shown that the direction of the permanent electric dipole moment of all these membranes reverses at different pH values in the range 3.2-6.4. The induced dipole moment and the retinal angle exhibit an increased value at these pHs. The results demonstrate that the bacteriorhodopsin protein makes an important contribution to the electrooptical properties of the purple membrane.

Hepatitis C Virus (HCV) non-structural protein 3 (NS3) protease drug resistance poses serious challenges on the design of an effective treatment. Substrate Envelope Hypothesis, "the substrates of HCV NS3/4A protease have a consensus volume inside the active site called substrate envelope" is used to design potent and specific drugs to overcome this problem. Using molecular docking, we studied the binding interaction of the different inhibitors and protein and evaluated the effect of three different mutations (R155K, D168A and A156V) on the binding of inhibitors. P2-P4 macrocycles of 5A/5B and modified 5A/5B hexapeptide sequences have the best scores against the wild-type protein -204.506 and -206.823 kcal/mole, respectively. Also, charged P2-P4 macrocycles of 3/4A and 4A/4B hexapeptide sequences have low scores with the wild-type protein -200.467 and -203.186 kcal/mole, respectively. R155K mutation greatly affects the conformation of the compounds inside the active site. It inverts its orientations, and this is because the large and free side chain of K155 which restricts the conformation of the large P2-P4 macrocycle. The conformation of charged P2-P4 macrocycle of 3/4A hexapeptide sequence in wild-type, A156V and D168A proteins is nearly equal; while that of charged P2-P4 macrocycle of 4A/4B hexapeptide sequence is different. Nevertheless, these compounds have a slight increase of Van der Waals volume compared to that of substrates, they are potent against mutations and have good scores. Therefore, the suggested drugs can be used as an effective treatment solving HCV NS3/4A protease drug resistance problem.

Based on the N-terminal hexapeptide product of hydrolysis (EDVVCC) at HCV NS5A/5B junction, three modified groups of compounds are built. The first group contains linear peptides while the second and third groups contain P1-P3 and P2-P4 macrocyclic structures, respectively. Quantitative Structure Activity Relationship (QSAR) characterization and docking simulations are performed in order to investigate the potential of these compounds as HCV NS3/4A protease inhibitors. Based on the QSAR properties, the three most stable compounds due to their lowest total energy are P1-P3 and P2-P4 macrocycles of azahexapeptide sequence (DDIVP vinyl amino cyclopropane) and P2-P4 macrocycle of azahexapeptide sequence (DDIVP norvaline). They also have high surface area, solvent accessible surface area, volume, molar refractivity and polarizabilty. They have moderately low dipole moment and good log P values, as well. The docking scores of the best two P2-P4 macrocycles are just acceptable. The two compounds 5A/5B hexapeptide sequence (DDIVP vinyl amino cyclopropane) and P2-P4 macrocycle of azapentapeptide sequence (DIVP vinyl amino cyclopropane) yielded the best docking scores.

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