Name
Abstract | ||
|---|---|---|
Incorporating backbone flexibility into protein ligand docking is still a challenging problem. In protein protein docking, normal mode analysis (NMA) has become increasingly popular as it can be used to describe the collective motions of a biological system, but the question of whether NMA can also be useful in predicting the conformational changes observed upon small-molecule binding has only been addressed in a few case studies. Here, we describe a large-scale study on the applicability of NMA for protein ligand docking using 433 apo/holo pairs of the Astex data sets. On the basis of sets of the first normal modes from the apo structure, we first generated for each paired holo structure a set of conformations that optimally reproduce its C-alpha trace with respect to the underlying normal mode subspace. Using Auto Dock, GOLD, and FlexX we then docked the original ligands into these conformations to assess how the docking performance depends on the number of modes used to reproduce the holo structure. The results of our study indicate that, even for such a best-case scenario, the use of normal mode analysis in small-molecule docking is restricted and that a general rule on how many modes to use does not seem to exist or at least is not easy to find. |
Year | DOI | Venue |
|---|---|---|
2012 | 10.1021/ci2004847 | JOURNAL OF CHEMICAL INFORMATION AND MODELING |
Field | DocType | Volume |
Searching the conformational space for docking,Docking (dog),Protein–ligand docking,Small molecule,Chemistry,Normal mode,Bioinformatics,AutoDock | Journal | 52 |
Issue | ISSN | Citations |
3 | 1549-9596 | 4 |
PageRank | References | Authors |
0.53 | 8 | 4 |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Matthias Dietzen | 1 | 9 | 1.36 |
| Elena Zotenko | 2 | 132 | 7.93 |
| Andreas Hildebrandt | 3 | 333 | 32.00 |
| Thomas Lengauer | 4 | 3155 | 605.03 |