On the diversity of physicochemical environments experienced by identical ligands in binding pockets of unrelated proteins.

Proteins
Abdullah KahramanJanet M Thornton

Abstract

Most function prediction methods that identify cognate ligands from binding site analyses work on the assumption of molecular complementarity. These approaches build on the conjectured complementarity of geometrical and physicochemical properties between ligands and binding sites so that similar binding sites will bind similar ligands. We found that this assumption does not generally hold for protein-ligand interactions and observed that it is not the chemical composition of ligand molecules that dictates the complementarity between protein and ligand molecules, but that the ligand's share within the functional mechanism of a protein determines the degree of complementarity. Here, we present for a set of cognate ligands a descriptive analysis and comparison of the physicochemical properties that each ligand experiences in various nonhomologous binding pockets. The comparisons in each ligand set reveal large variations in their experienced physicochemical properties, suggesting that the same ligand can bind to distinct physicochemical environments. In some protein ligand complexes, the variation was found to correlate with the electrochemical characteristic of ligand molecules, whereas in others it was disclosed as a prerequisit...Continue Reading

References

Dec 1, 1991·Journal of Computer-aided Molecular Design·G E KelloggD J Abraham
Oct 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·M R Gunner, B Honig
Jun 1, 1989·Journal of Molecular Graphics·G Náray-Szabó
Jun 20, 1988·Journal of Molecular Biology·M Levitt, M F Perutz
Jan 16, 1986·Nature·D Eisenberg, A D McLachlan
Nov 19, 1974·Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character·A R Fersht
May 26, 1995·Science·B Honig, A Nicholls
Oct 1, 1994·Journal of Computer-aided Molecular Design·P L Chau, P M Dean
Oct 1, 1994·Journal of Computer-aided Molecular Design·P L Chau, P M Dean
Oct 1, 1993·Journal of Computer-aided Molecular Design·W HeidenJ Brickmann
Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·P S LedvinaF A Quiocho
May 2, 1997·Journal of Molecular Biology·A J McCoyP M Colman
Sep 23, 1997·Journal of Molecular Biology·H A GabbM J Sternberg
Oct 7, 1998·Protein Science : a Publication of the Protein Society·J LiangC Woodward
Oct 27, 1998·Trends in Biochemical Sciences·K Henrick, J M Thornton
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Dec 11, 1999·Nucleic Acids Research·A Bairoch
Feb 19, 2000·Journal of Molecular Recognition : JMR·P E Smith, J J Tanner
Feb 13, 2001·Biophysical Journal·R LuoM K Gilson
Feb 24, 2001·Proceedings of the National Academy of Sciences of the United States of America·C R LancasterA Kröger
Mar 29, 2001·Nature Structural Biology·A M BilwesM I Simon
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·N A BakerJ A McCammon
Aug 5, 1997·Chemical Reviews·Robert E. Babine, Steven L. Bender
Aug 5, 1997·Chemical Reviews·Peter WallimannFrançois Diederich
Mar 1, 2003·Science·Leo C JamesDan S Tawfik
Mar 26, 2003·Journal of Chemical Information and Computer Sciences·Christoph SteinbeckEgon Willighagen
Mar 26, 2003·Biochemistry·Dennis R LivesayShankar Subramaniam
Jun 26, 2003·Nucleic Acids Research·T Andrew BinkowskiJie Liang
Jul 25, 2003·Trends in Biochemical Sciences·Leo C James, Dan S Tawfik

❮ Previous
Next ❯

Citations

Sep 15, 2011·Journal of Computer-aided Molecular Design·Laurence Leherte, Daniel P Vercauteren
Jun 29, 2013·Journal of Computer-aided Molecular Design·Matthias WirthWolfgang H B Sauer
Jan 25, 2012·Journal of Structural and Functional Genomics·Lee SaelDaisuke Kihara
Aug 28, 2012·Journal of Chemical Information and Modeling·Noé SturmEsther Kellenberger
Feb 5, 2013·Journal of the American Chemical Society·Emmanuel S BurgosVern L Schramm
Jun 15, 2011·Bioinformatics·Abdullah KahramanRuedi Aebersold
Jan 22, 2013·Bioinformatics·Mu Gao, Jeffrey Skolnick
Nov 28, 2012·BMC Bioinformatics·Gregory M CiprianoMichael Gleicher
Nov 10, 2013·PLoS Computational Biology·Mu Gao, Jeffrey Skolnick
Apr 26, 2014·PLoS Computational Biology·Grace W Tang, Russ B Altman
Sep 27, 2013·PloS One·Abdullah KahramanLars Malmström
Oct 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Shivas R AminOlivier Lichtarge
Aug 29, 2014·International Journal of Molecular Sciences·Bingjie HuDaisuke Kihara
Mar 1, 2011·Current Opinion in Structural Biology·Serkan ErdinOlivier Lichtarge
Oct 1, 2015·ACS Chemical Biology·Sarah BarelierBrian K Shoichet
Jun 15, 2010·Proteins·Lorna J SmithJanet M Thornton
Sep 24, 2014·Journal of Biomolecular Structure & Dynamics·S Usha, S Selvaraj
Jun 21, 2012·Biophysical Journal·Sankar BasuRahul Banerjee
Mar 11, 2018·BMC Bioinformatics·Rajiv Gandhi Govindaraj, Michal Brylinski
Aug 9, 2019·MedChemComm·Christiane EhrtOliver Koch
Dec 1, 2020·Computational and Structural Biotechnology Journal·Mireia Rosell, Juan Fernández-Recio
Aug 11, 2018·ACS Chemical Biology·Joshua PottelBrian K Shoichet

❮ 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.