Question

1. what is hydrophobic effect? please provide your answer in the context of drug-target intereactions.

2. Discuss thermodynamics of binding (i.e. discuss thermodynamic parameters that affect affinity). How do these parameters are affected by the hydrophobic effect?

3. suggest an experiment to dissect the contribution of these parameters and briefly describe it/

Answer 1

1. Hydrophobic effect is influence of non-polar interactions within a system or between two systems towards stabilization of the structure. In the drug-target interactions, the drug is designed in the fashion wherein, it has hydrophobic groups attached to it, which are attracted towards the target molecules, which are protein structures with hydrophobic groups on it.

2. As the hydrophobic interactions between the drug and the target improves, the thermodynamic free energy decreases, that is the system becomes more stable. This shows that the drug is more effective in controling the target activity. So, a stronger hydrophobicity in the drug would have better or stronger affinity (defined by strength of hydrophobic interaction) for the target in the biological system.

3. An experiment to understand this phenomenon can be designed. First the drug is modified to have polar groups on it (less interaction with the target). It is fed to the target cells. Indicator is added to study the apoptosis. The results are noted down of number of cell deaths in a given time. Now the drug with non-polar groups which can have better hydrophobic interaction with the target is designed and fed to the cells in the same fashion. The number of cell deaths are noted down in a similar manner. The number of cell deaths are compared with the first experiment which would be greater in this case.