Active-site-directed 3D database searching: pharmacophore extraction and validation of hits

Journal of Computer-aided Molecular Design
D E ClarkC M Murray

Abstract

Two new computational tools, PRO_PHARMEX and PRO_SCOPE, for use in active-site-directed searching of 3D databases are described. PRO_PHARMEX is a flexible, graphics-based program facilitating the extraction of pharmacophores from the active site of a target macromolecule. These pharmacophores can then be used to search a variety of databases for novel lead compounds. Such searches can often generate many 'hits' of varying quality. To aid the user in setting priorities for purchase, synthesis or testing, PRO_SCOPE can be used to dock molecules rapidly back into the active site and to assign them a score using an empirical scoring function correlated to the free energy of binding. To illustrate how these tools can add value to existing 3D database software, their use in the design of novel thrombin inhibitors is described.

References

Dec 1, 1992·Journal of Computer-aided Molecular Design·H J Böhm
Sep 1, 1992·Journal of Chemical Information and Computer Sciences·G KlopmanD M Balthasar
Jul 1, 1992·Medicinal Research Reviews·M D Walkinshaw
Feb 1, 1992·Journal of Computer-aided Molecular Design·H J Böhm
Jun 12, 1992·Journal of Medicinal Chemistry·Y C Martin
Oct 1, 1991·Journal of Computer-aided Molecular Design·C A Pepperrell, P Willett
Mar 1, 1989·Journal of Computer-aided Molecular Design·R A DammkoehlerG R Marshall
Apr 1, 1987·Journal of Computer-aided Molecular Design·D MayerG R Marshall
Jun 1, 1986·Journal of Medicinal Chemistry·R P SheridanR Venkataraghavan
Oct 25, 1982·Journal of Molecular Biology·I D KuntzT E Ferrin
Sep 1, 1993·Protein Engineering·B K Shoichet, I D Kuntz
Jun 1, 1994·Journal of Cardiothoracic and Vascular Anesthesia·J BoldtG Hempelmann
Apr 1, 1995·Journal of Computer-aided Molecular Design·R C Glen, A W Payne
Feb 1, 1995·Journal of Computer-aided Molecular Design·D E ClarkD R Westhead
Jun 9, 1995·Journal of Medicinal Chemistry·M Hahn
Jun 1, 1994·Journal of Computer-aided Molecular Design·E C MengG E Kellogg
Apr 1, 1994·Journal of Computer-aided Molecular Design·M D MillerR P Sheridan
Feb 1, 1993·Journal of Computer-aided Molecular Design·Y C MartinP A Pavlik
Oct 1, 1993·Journal of Computer-aided Molecular Design·E E HodgkinM Whittaker
Jul 1, 1993·Journal of Chemical Information and Computer Sciences·M C NicklausD Zaharevitz
Mar 5, 1993·Science·B K ShoichetK M Perry
Apr 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·C S RingF E Cohen
Dec 22, 1995·Journal of Medicinal Chemistry· Ajay, M A Murcko
Jan 1, 1996·Journal of Chemical Information and Computer Sciences·D E ClarkC W Murray
Oct 1, 1995·Journal of Computer-aided Molecular Design·C W MurrayD G Byrne
May 1, 1996·Journal of Chemical Information and Computer Sciences·D BarnumP Sprague
Feb 1, 1996·Journal of Computer-aided Molecular Design·P D Grootenhuis, M Karplus
Dec 1, 1995·Journal of Computer-aided Molecular Design·R A DammkoehlerG R Marshall
Dec 1, 1995·Journal of Computer-aided Molecular Design·G JonesR C Glen
Jul 1, 1995·Acta Crystallographica. Section D, Biological Crystallography·P D Grootenhuis, P J van Galen

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.