Ligand placement based on prior structures: the guided ligand-replacement method.

ABSTRACT: The process of iterative structure-based drug design involves the X-ray crystal structure determination of upwards of 100 ligands with the same general scaffold (i.e. chemotype) complexed with very similar, if not identical, protein targets. In conjunction with insights from computational models and assays, this collection of crystal structures is analyzed to improve potency, to achieve better selectivity and to reduce liabilities such as absorption, distribution, metabolism, excretion and toxicology. Current methods for modeling ligands into electron-density maps typically do not utilize information on how similar ligands bound in related structures. Even if the electron density is of sufficient quality and resolution to allow de novo placement, the process can take considerable time as t

SUBMITTER: Klei HE 

PROVIDER: S-EPMC3919265 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature