Name
Title | ||
|---|---|---|
An improved relaxed complex scheme for receptor flexibility in computer-aided drug design. |
Abstract | ||
|---|---|---|
The interactions among associating (macro)molecules are dynamic, which adds to the complexity of molecular recognition. While
ligand flexibility is well accounted for in computational drug design, the effective inclusion of receptor flexibility remains
an important challenge. The relaxed complex scheme (RCS) is a promising computational methodology that combines the advantages
of docking algorithms with dynamic structural information provided by molecular dynamics (MD) simulations, therefore explicitly
accounting for the flexibility of both the receptor and the docked ligands. Here, we briefly review the RCS and discuss new
extensions and improvements of this methodology in the context of ligand binding to two example targets: kinetoplastid RNA
editing ligase 1 and the W191G cavity mutant of cytochrome c peroxidase. The RCS improvements include its extension to virtual screening, more rigorous characterization of local and
global binding effects, and methods to improve its computational efficiency by reducing the receptor ensemble to a representative
set of configurations. The choice of receptor ensemble, its influence on the predictive power of RCS, and the current limitations
for an accurate treatment of the solvent contributions are also briefly discussed. Finally, we outline potential methodological
improvements that we anticipate will assist future development. |
Year | DOI | Venue |
|---|---|---|
2008 | 10.1007/s10822-007-9159-2 | Journal of computer-aided molecular design |
Keywords | Field | DocType |
Clustering,Docking,Ensemble-based docking,Kinetoplastid RNA editing ligase 1,Molecular dynamics,Non-redundant ensemble,Protein–ligand binding,Relaxed complex method,Representative ensemble,Virtual screening,W191G cytochrome,c,peroxidase | Molecular recognition,Computer-aided,Docking (dog),Computer Aided Design,Chemistry,Molecular dynamics,Bioinformatics,Macro,Cluster analysis,Virtual screening | Journal |
Volume | Issue | ISSN |
22 | 9 | 0920-654X |
Citations | PageRank | References |
39 | 2.68 | 13 |
Authors | ||
3 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Rommie E Amaro | 1 | 110 | 15.54 |
| Riccardo Baron | 2 | 98 | 9.23 |
| J. Andrew Mccammon | 3 | 156 | 16.58 |