Notes
Slide Show
Outline
1
Towards All-Electron Description of Biomolecular Systems: Estimating the Binding Affinity in the Target-Ligand Complexes
2
"Predicting the binding affinity between..."
  • Predicting the binding affinity between a target and a ligand forming a non-covalent complex is a very challenging task that has been pursued for decades.


  • Computer-aided structure-based methods are aimed at predicting the binding mode of a ligand in the binding site of a protein or any molecular target and at obtaining an estimate of the binding affinity.


  • These methods involve two computational steps: docking and scoring.
  • .


3
"In the docking step,"
  • In the docking step, multiple protein-ligand configurations are generated.


  • Then, a scoring function is used to calculate the affinity between the receptor and the ligand for each configuration


  • Requirements for the scoring function:
  • 1) Binding free energies for each configuration need to be estimated accurately
  • 2) A scoring function must be sufficiently fast to be applied in a docking algorithm.


4
Assessment of the Available Scoring Functions
5
Application of Semi-Empirical Quantum Chemical Methods as Scoring Function in Docking
6
Application of Semi-Empirical Quantum Chemical Methods as Scoring Function in Docking
7
Computational Method
8
Model Systems
  • Theophylline-binding RNA aptamer


  • Trypsin and a series of closely related inhibitors


  • Influenza virus neuramindase (wild + mutants) and its three inhibitors
9
 
10
 
11
 
12
Calculation Times
13
 
14
 
15
 
16
 
17
 
18
Conclusions
19
Conclusions