Benefits of Structural Genomics for Drug Discovery Research
While three dimensional structures have long been used to search for new drug targets, only a fraction of new drugs coming to the market has been developed with the use of a structure-based drug discovery approach. However, the recent years have brought not only an avalanche of new macromolecular structures, but also significant advances in the protein structure determination methodology only now making their way into structure-based drug discovery. In this paper, we review recent developments resulting from the Structural Genomics (SG) programs, focusing on the methods and results most likely to improve our understanding of the molecular foundation of human diseases. SG programs have been around for almost a decade, and in that time, have contributed a significant part of the structural coverage of both the genomes of pathogens causing infectious diseases and structurally uncharacterized biological processes in general. Perhaps most importantly, SG programs have developed new methodology at all steps of the structure determination process, not only to determine new structures highly efficiently, but also to screen protein/ligand interactions. We describe the methodologies, experience and technologies developed by SG, which range from improvements to cloning protocols to improved procedures for crystallographic structure solution that may be applied in 'traditional' structural biology laboratories particularly those performing drug discovery. We also discuss the conditions that must be met to convert the present high-throughput structure determination pipeline into a high-output structure-based drug discovery system.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 980036
- Report Number(s):
- BNL-92954-2010-JA; TRN: US201015%%1421
- Journal Information:
- Infectious Disorders - Drug Targets, Vol. 9, Issue 5
- Country of Publication:
- United States
- Language:
- English
Similar Records
Structural Genomics and Drug Discovery for Infectious Diseases
AutoDrug: fully automated macromolecular crystallography workflows for fragment-based drug discovery
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE
BIOLOGY
CLONING
DISEASES
DRUGS
FOCUSING
FOUNDATIONS
HUMAN POPULATIONS
INFECTIOUS DISEASES
INTERACTIONS
LABORATORIES
MARKET
PATHOGENS
PIPELINES
PROTEIN STRUCTURE
RANGE
REVIEWS
SCREENS
SOLUTIONS
TARGETS
USES
national synchrotron light source