Receptor pharmacophore ensemble (REPHARMBLE): a probabilistic pharmacophore modeling approach using multiple protein-ligand complexes

Journal of Molecular Modeling
Sivakumar Prasanth Kumar

Abstract

Ensemble methods are gaining more importance in structure-based approaches as single protein-ligand complexes strongly influence the outcomes of virtual screening. Structure-based pharmacophore modeling based on a single protein-ligand complex with complex feature combinations is often limited to certain chemical classes. The REPHARMBLE (receptor pharmacophore ensemble) approach presented here examines the ability of an ensemble of selected protein-ligand complexes to populate pharmacophore space in the ligand binding site, rigorously assesses the importance of pharmacophore features using Poisson statistic and information theory-based entropy calculations, and generates pharmacophore models with high probabilities. In addition, an ensemble scoring function that combines all the resultant high-scoring pharmacophore models to score molecules is derived. The REPHARMBLE approach was evaluated on ten DUD-E benchmark datasets and afforded good screening performance, as measured by receiver operating characteristic, enrichment factor and Güner-Henry score. Although one of the high-scoring models achieved superior statistical results in each dataset, the ensemble scoring function balanced the shortcomings of each model and passed with...Continue Reading

References

Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Aug 7, 2002·Current Opinion in Structural Biology·Roland L Dunbrack
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Sep 3, 2004·Journal of Medicinal Chemistry·Steffen Renner, Gisbert Schneider
Nov 30, 2004·Journal of Medicinal Chemistry·Jeremy L JenkinsJohn W Davies
Jan 26, 2005·Journal of Chemical Information and Modeling·Gerhard Wolber, Thierry Langer
Feb 7, 2006·Journal of Molecular Graphics & Modelling·Junmei WangDavid A Case
May 23, 2006·Journal of Chemical Information and Modeling·Jun FengS Stanley Young
Nov 28, 2006·Journal of Chemical Information and Modeling·Jing Chen, Luhua Lai
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
May 21, 2009·Journal of Chemical Information and Modeling·Tim ten Brink, Thomas E Exner
Sep 19, 2009·Journal of Chemical Information and Modeling·Noeris K SalamWoody Sherman
Sep 2, 2010·Journal of Chemical Information and Modeling·Oliver KorbThomas E Exner
Aug 27, 2011·Journal of Chemical Information and Modeling·Marijn P A SandersJan P G Klomp
Sep 29, 2011·Nucleic Acids Research·Anna GaultonJohn P Overington
Oct 11, 2011·Journal of Cheminformatics·Noel M O'BoyleGeoffrey R Hutchison
Dec 14, 2011·Journal of Chemical Information and Modeling·Fredrik SvenssonChristian Sköld
Apr 7, 2012·Journal of Chemical Information and Modeling·Jamel MeslamaniDidier Rognan
Jun 1, 2012·Journal of Chemical Information and Modeling·Marijn P A SandersAlberto Del Rio
Jun 22, 2012·Journal of Medicinal Chemistry·Michael M MysingerBrian K Shoichet
Sep 14, 2012·Journal of Chemical Information and Modeling·Simon CrossGabriele Cruciani
May 9, 2013·Current Topics in Medicinal Chemistry·Rodolpho C Braga, Carolina H Andrade
Nov 20, 2013·Journal of Chemical Information and Modeling·Rafał Kurczab, Andrzej J Bojarski
Apr 4, 2014·Journal of Cheminformatics·Stefan BietzMatthias Rarey
Jan 7, 2015·Journal of Chemical Information and Modeling·Thomas SanderChristian Rufener
Nov 18, 2015·Journal of Chemical Theory and Computation·James A MaierCarlos Simmerling
Dec 3, 2016·Nucleic Acids Research·UNKNOWN The UniProt Consortium
Apr 26, 2017·Journal of Biotechnology·I SchomburgD Schomburg
Sep 10, 2017·Journal of Computer-aided Molecular Design·Polo C-H LamMaxim Totrov

❮ Previous
Next ❯

Citations

Sep 12, 2019·Journal of Receptor and Signal Transduction Research·Chirag N PatelHimanshu A Pandya
Apr 9, 2020·Frontiers in Cellular and Infection Microbiology·Congshan LiuHaobing Zhang
Jun 15, 2021·Journal of Chemical Information and Modeling·Michel F SannerEwa Lis

❮ 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.