Challenges In Drug Discovery

Question

[Flow]

It is 2012 but many of the inherent problems of in-silico drug discovery methods have not been resolved yet, such as; accuracte prediction of binding affinities, receptor flexibility, free energy calculation, realistic scoring functions, etc, to name a few. So these could be considered, as of today, as the main challenges of drug discovery methods, which should be solved in the forthcoming years.

Nevertheless, let's suppose that those questions have been more or less solved or improved. In such a hypothetical situation, what do you think would be the next challenging questions in drug discovery (mostly related with in silico methods)?

Answer 1

[miquelduranfrigola]

In my opinion, the big challenges are:

• Personalized medicine: Pharmacogenomics, i.e. how genomic variants affect drug response.
• Polypharmacology: Design drugs that are able to perturb a network better than a single target (magic shotguns instead of magic bullets).
• Drug repositioning or repurposing: Using old drugs for new purposes.
• Drug combinations: Combine more than one drug to obtain synergistic effects, most likely approached with biological network analysis.
• Systems chemical biology: Start understand pharmacodynamics and pharmacokinetics form a systems biology perspective.
• Targeting protein-protein interactions: This is usually difficult, since interfaces are not as hydrophobic as binding pockets.
• Target profiling: Use chemogenomics to know the full target profile (pharmacological profile) of drugs.

And I'm sure there are more!

[Flow]

Really interesting answer. Now I am trying to find top related papers.