Computational chemistry approaches to drug discovery in signal transduction

Biotechnology Journal
Peter M Fischer

Abstract

The advent of therapeutic strategies aimed at targeting specific macromolecular components of deregulated signaling pathways associated with particular disease states has given rise to the idea that it should be possible to design ligands as drug candidates to these targets from first principles. This concept has been beckoning for a long time but structure-based ligand design only became feasible once it was possible to determine the 3-D structures of molecular targets at atomic resolution. However, structure-based design turned out to be difficult, chiefly because under physiological conditions both receptors and ligands are not static but they behave dynamically. While it is possible to design ligands with high steric and electronic complementarity to a receptor site, it is always uncertain how biologically relevant the assumed conformations of both ligand and receptor actually are. The fact that it remains beyond our current abilities to predict with sufficient accuracy the affinity between hypothetical ligand and receptor poses is in part connected with this problem and continues to confound the reliable prediction of drug-like ligands for therapeutic targets. Nevertheless, significant progress has been made and so-called ...Continue Reading

References

Oct 24, 1995·Proceedings of the National Academy of Sciences of the United States of America·A Qu, D J Leahy
Nov 1, 1995·Proteins·A SaliM Karplus
Jan 1, 1996·Medicinal Research Reviews·R S BohacekW C Guida
Jan 1, 1996·Journal of Pharmaceutical Sciences·K PalmP Artursson
Feb 21, 1997·Journal of Molecular Biology·R M KnegtelC M Oshiro
Sep 16, 1998·Current Opinion in Chemical Biology·A S Ripka, D H Rich
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·I D KuntzP A Kollman
Sep 24, 1999·Journal of Molecular Biology·J KallenU Hommel
Aug 5, 2000·Science·K PalczewskiM Miyano
Mar 10, 2001·Nature·G Jimenez-SanchezD Valle
May 17, 2001·Proceedings of the National Academy of Sciences of the United States of America·M ShimaokaT A Springer
Jan 29, 2002·Combinatorial Chemistry & High Throughput Screening·J Aqvist, J Marelius
May 9, 1996·Chemical Reviews·Mati KarelsonAlan R. Katritzky
Mar 26, 2002·Journal of Chemical Information and Computer Sciences·Xueliang Fang, Shaomeng Wang
May 16, 2002·Journal of the American Chemical Society·Jung-Hsin LinJ Andrew McCammon
May 17, 2002·Journal of Medicinal Chemistry·Angelo Vedani, Max Dobler
May 17, 2002·Journal of Medicinal Chemistry·Thompson N DomanBrian K Shoichet
May 31, 2002·Journal of Medicinal Chemistry·Daniel F VeberKenneth D Kopple
Jul 12, 2002·Journal of Medicinal Chemistry·Matthew D KrasowskiNeil L Harrison
Jul 13, 2002·Journal of Computational Chemistry·Yuan-Ping PangFranklyn G. Prendergast
Aug 29, 2002·Journal of Computer-aided Molecular Design·Renxiao WangShaomeng Wang
Sep 5, 2002·Nature Reviews. Drug Discovery·Andrew L Hopkins, Colin R Groom
Sep 5, 2002·Proteins·Natasja BrooijmansIrwin D Kuntz
Sep 6, 2002·Journal of Medicinal Chemistry·Yvonne C MartinLinda M Traphagen
Oct 17, 2002·Journal of Molecular Biology·Patrice Koehl, Michael Levitt
Nov 26, 2002·Journal of Chemical Information and Computer Sciences·Joseph L DurantJames G Nourse
Jan 28, 2003·Journal of Chemical Information and Computer Sciences·Xuan Hong, A J Hopfinger
Jan 28, 2003·Drug Discovery Today·Robert P Sheridan, Simon K Kearsley
Feb 8, 2003·Annual Review of Biophysics and Biomolecular Structure·Natasja Brooijmans, Irwin D Kuntz
Mar 21, 2003·Medicinal Research Reviews·Ingo Muegge
Mar 26, 2003·Journal of Computer-aided Molecular Design·Christopher W Murray, Marcel L Verdonk
Mar 26, 2003·Journal of Chemical Information and Computer Sciences·Edmond AbrahamianRobert D Clark
May 30, 2003·Journal of Medicinal Chemistry·Renxiao WangShaomeng Wang

❮ Previous
Next ❯

Citations

Dec 14, 2012·Journal of the Royal Society, Interface·Panagiotis L Kastritis, Alexandre M J J Bonvin
Dec 15, 2010·International Journal of Molecular Sciences·Kyaw Zeyar Myint, Xiang-Qun Xie
Sep 1, 2009·Expert Opinion on Drug Discovery·Sharangdhar S PhatakClaudio N Cavasotto
Apr 17, 2008·Biotechnology Journal·Lodewijk Dekker
Feb 12, 2010·Journal of Computer-aided Molecular Design·Chin Yee LiewChun Wei Yap
Mar 10, 2009·Journal of Chemical Information and Modeling·Chin Y LiewChun W Yap

❮ 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.

Related Papers

Briefings in Bioinformatics
Georgios A DalkasSophia Kossida
Combinatorial Chemistry & High Throughput Screening
Tianyun LiuEmidio Capriotti
© 2022 Meta ULC. All rights reserved