ISSN:
1573-5001
Keywords:
dihydrofolate reductase
;
ligand docking
;
protein–ligand complexes
;
structure determination
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
Notes:
Abstract A new method is proposed for docking ligands into proteins in cases where an NMR-determined solution structure of a related complex is available. The method uses a set of experimentally determined values for protein–ligand, ligand–ligand, and protein–protein restraints for residues in or near to the binding site, combined with a set of protein–protein restraints involving all the other residues which is taken from the list of restraints previously used to generate the reference structure of a related complex. This approach differs from ordinary docking methods where the calculation uses fixed atomic coordinates from the reference structure rather than the restraints used to determine the reference structure. The binding site residues influenced by replacing the reference ligand by the new ligand were determined by monitoring differences in 1H chemical shifts. The method has been validated by showing the excellent agreement between structures of L. casei dihydrofolate reductase.trimetrexate calculated by conventional methods using a full experimentally determined set of restraints and those using this new restraint docking method based on an L. casei dihydrofolate reductase.methotrexate reference structure.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008379225053
Permalink
