Prova de funcionament SS + YT

1. Molecular Docking G. Schaftenaar

8. Simulated Annealing Finding a global minimium by lowering the temperature during the Monte Carlo/MD simulation

19. Empirical scoring Loss of entropy during binding Hydrogen-bonding Ionic interactions Aromatic interactions Hydrophobic interactions rot rot N G G G       0         bonds H neutral hb R f G . ,          . , int ionic io R f G         int arom arom R f G . ,         . . , cont lipo lipo R f G 

22. Distribution of interatomic distances is converted into energy functions by inverting Boltzmann’s law. F P (N,O)

23. Potential of Mean Force (PMF)                 ij seg i corr Vol B ij r r f T k r F  _ ln   r ij seg  Number density of atom pairs of type ij at atom pair distance r Number density of atom pairs of type ij in reference sphere with radius R ij bulk  ij bulk 

26. Concluding remarks Although the reliability of docking methods is not so high, they can provide new suggestions for protein-ligand interactions that otherwise may be overlooked Scoring functions are the Achilles’ heel of docking programs . False positives rates can be reduced using several scoring functions in a consensus-scoring strategy