|
|
|
|
|
|
| Willem Nissink, Cambridge Crystallographic Data Centre |
|
Willem Nissink is a senior software developer at the Cambridge Crystallographic Data Centre (CCDC) and manages the GOLD and SuperStar software projects. A Dutch national, he has a PhD from Utrecht University. Before moving to the CCDC at the start of 2001, he worked in a post-doc position in the group of Professor Gerhard Klebe (Marburg, Germany) on knowledge-based ligand superimposition methods. Current research interests include scoring functions for protein-ligand docking, validation of docking performance, and knowledge-based prediction of molecular interactions.
|
|
Exploiting protein-specific information in docking
Willem Nissink, Cambridge Crystallographic Data Centre, 12 Union Road Cambridge, Cambs, CB2 1EZ , United Kingdom
State-of-the-art software docking tools nowadays allow the user to dock ligands with reasonable confidence. Still, it is clear that our scoring functions are not perfect, and often overlook weak interactions like CH...O hydrogen bonds completely. Neither is it straightforward to take into account binding site information, although such knowledge can be quite obvious for individual targets. Examples of the latter are e.g. knowledge about displaceable mediating waters; placement of a common ligand scaffold; metal coordination geometries, or presence of flexible side-chains.
In this talk we will discuss developments that enable easy use of additional knowledge, either during docking, or, a posteriori, through post-processing tools. We will show the approach used for inclusion of water information in GOLD, and present results for the automatic assessment of water-mediated
binding modes during docking. We will show improvements to the handling of metals, and docking restraints. Further we will introduce our newly developed post-processing tool, SILVER, that allows the user to set up target-specific filters using a variety of contact- and hydrogen-bond descriptors.
|
|
|
|
|
|
|
|
|
