Re: Nice one judge
"Some of that is down to old-school (out of date) thinking on the part of synthetic and medicinal chemists"
Well I know what you mean but after 38 years of hoping that we'd be able to model reality sufficiently well to do most drug discovery in a computer I think we are still far from it.
The reasons are too many and varied for this forum but include :
1) The conformational flexibility of small molecules
2) The structural complexities of target molecules even when the structure is 'known' *
3) Even with a good structure to work with the reality is often far more complex with the target protein being actually in a different state or set of states in the physiological condition so that 'docking' of drug targets to the target is rendered useless.
4) Even if a set of algorithms could 'solve' 1 & 2 ALL the other criteria necessary for a safe, useful drug in terms of adsorption, metabolism, toxicity still need to be met - most drug leads fail here
* - the gold standard for structure determination is x-ray but this is done in the 'solid' state usually at low temperatures and that masks the kinetic and water effects seen in 'real ' situations.
I've seen vast advances in the area of computing being applies to medicinal chemistry but even in my own field of protein modeling there is still a LONG way to go.