Fragment-based lead discovery

Published on September 23, 2013   46 min

A selection of talks on Pharmaceutical Sciences

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Today I'm going to tell you about an approach to drug discovery called fragment-based lead discovery, which has really started coming to preeminence in the past decade or so.
My presentation is in three parts. The first is an introduction to the concept of fragment-based lead discovery as well as some of the problems that can arise. And then I'm going to tell you about methods to find, as well as evaluate fragments, and close by giving you a few examples of how this has been successfully applied as well as for other resources.
A prior talk in the series was devoted to high throughput screening. And you can think about high throughput screening as trying to guess a word by making all possible combinations of letters. And if you screen through enough word combinations, you'll eventually be able to discover your ligand. In the case of fragment-based approaches, rather than trying to explore all possible combinations of say, six letters, you would look for individual word fragments, for example, a LIG and an AND, and then link those together to find your ligand. Or, more commonly, you might find a single-word fragment, say a LIG, and then grow that letter by letter into your final ligand.
To understand why this process is more efficient, it helps to think of Scrabble. Those of you who are serious players will know that there are exactly 96 two-letter words that are permissible. However, if you add one letter, the number of possibilities increases by more than an order of magnitude.