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SUMMARY:Identification and characterization of interaction sites with MD s
 imulations of mixed solvents – Application to non-standard targets - Pro
 fessor Xavier Barril\, ICREA Research Professor at Barcelona University\, 
 Spain
DTSTART:20141112T101500Z
DTEND:20141112T111500Z
UID:TALK55582@talks.cam.ac.uk
CONTACT:23791
DESCRIPTION:Structure-based methods use 3D information of the receptor as 
 a mold to design molecules that\, by placing complementary chemical groups
  at the right locations\, can become efficient ligands. Pre-calculated pot
 entials are of great help in ligand design because they inform about which
  moieties are more adequate at each spot. However\, complex aspects of mol
 ecular recognition\, such as protein flexibility and the effect of aqueous
  solvation degrade the quality of the predictions. This is particularly tr
 ue for polar contacts\, as they can have completely different behavior dep
 ending on the local environment and the existence of distinct hydration pa
 tterns. I will present MDmix (Molecular Dynamics simulations with mixed so
 lvents) as a method to obtain atom-specific interaction free energy maps\,
  taking explicit account of aqueous solvation and protein flexibility. MDm
 ix not only reproduces experimentally-derived pharmacophores but also info
 rms about hydration patterns and provides a direct evidence of water displ
 aceability. Hence\, the method tackles two problems that are usually dealt
  with separately\, providing more accurate interaction maps than ordinary 
 interaction potentials (e.g. GRID) and more quantitative water displacemen
 t measures than inhomogeneous fluid solvation theory (WaterMap). This tool
  is being used in my group to exploit novel binding sites that give access
  to non-standard molecular mechanisms of action\, such as alteration of pr
 otein-protein complexes\, pharmacological chaperoning or allosterism.\n\nh
 ttp://pubs.acs.org/doi/abs/10.1021/jm5010418 
LOCATION:Biochemistry Seminar Room\, Sanger Building
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