Molecular Jigsaws @ Quest Compbio
Pipelines that just fit

Oct 12

The molecular complexity argument

This is a post that introduces the idea of molecular complexity and FBLD. In 2001, Hann and colleagues GSK developed the theory of molecular complexity, an idea that largely revolves around the principle that simpler molecules can be accommodated in a variety of protein sites compared to their more complex counterparts. The fact that molecular simplicity is inherently linked to molecular size meant that the tenet of molecular complexity could provide a likely explanation for successes within....
Oct 12

Target druggability

How does one really assess druggability of a particular target?   Besides the possession of clear disease relevance, druggability is another important factor in target selection within drug discovery. Druggability in the context of drug discovery is often reduced to the ability or the potential to be able to discover small-molecule binders to the particular target.   In terms of assessing this property, there are a few different methodologies, of which the first is the....
Oct 12

Free energy perturbation

This post deals with the free energy perturbation technique.    The free energy change associated with the transformation of a state A to B can be calculated with FEP, a method based on a formulation by Zwanzig in 1954. This transformation is performed by treating the end state B as a perturbation on state A.   The potential energy of state B is calculated from a simulation on state A. For such a calculation to be accurate the state B must also be adequately sampled from a simulation of state....