Structure-driven fragment-based (SDFB) approaches have provided efficient methods for the identification of novel drug candidates. This strategy has been largely applied in discovering several pharmacological ligand classes, including enzyme inhibitors, receptor antagonists and, more recently, also allosteric (positive and negative) modulators. Recently, Siegal and collaborators reported an interesting study, performed on a detergent-solubilized StaR adenosine A2A receptor, describing the existence of both fragment-like negative allosteric modulators (NAMs), and fragment-like positive allosteric modulators (PAMs). From this retrospective study, our results suggest that Supervised Molecular Dynamics (SuMD) simulations can support, on a reasonable time scale, the identification of fragment-like PAMs following their receptor recognition pathways and characterizing the possible allosteric binding sites.
|Number of pages||12|
|Publication status||Published - 16 May 2017|
Bibliographical noteThis is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- adenosine receptors
- positive allosteric modulators
- fragment-based approaches
- supervised molecular dynamics