Multiple grid arrangement improves ligand docking with unknown binding sites: Application to the inverse docking problem

Computational Biology and Chemistry
Tomohiro BanYutaka Akiyama

Abstract

The identification of comprehensive drug-target interactions is important in drug discovery. Although numerous computational methods have been developed over the years, a gold standard technique has not been established. Computational ligand docking and structure-based drug design allow researchers to predict the binding affinity between a compound and a target protein, and thus, they are often used to virtually screen compound libraries. In addition, docking techniques have also been applied to the virtual screening of target proteins (inverse docking) to predict target proteins of a drug candidate. Nevertheless, a more accurate docking method is currently required. In this study, we proposed a method in which a predicted ligand-binding site is covered by multiple grids, termed multiple grid arrangement. Notably, multiple grid arrangement facilitates the conformational search for a grid-based ligand docking software and can be applied to the state-of-the-art commercial docking software Glide (Schrödinger, LLC). We validated the proposed method by re-docking with the Astex diverse benchmark dataset and blind binding site situations, which improved the correct prediction rate of the top scoring docking pose from 27.1% to 34.1%; ...Continue Reading

References

Jan 1, 1990·Proteins·D S Goodsell, A J Olson
Oct 25, 1982·Journal of Molecular Biology·I D KuntzT E Ferrin
Jan 1, 1996·Journal of Molecular Recognition : JMR·D S GoodsellA J Olson
Apr 4, 1997·Journal of Molecular Biology·G JonesR Taylor
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Mar 19, 2004·Journal of Medicinal Chemistry·Richard A FriesnerPeter S Shenkin
Mar 19, 2004·Journal of Medicinal Chemistry·Thomas A HalgrenJay L Banks
Aug 3, 2004·Nature Reviews. Drug Discovery·Ted T Ashburn, Karl B Thor
Jul 18, 2006·Nucleic Acids Research·Honglin LiHualiang Jiang
Feb 16, 2007·Journal of Medicinal Chemistry·Michael J HartshornChristopher W Murray
Jan 10, 2008·Journal of Computer-aided Molecular Design·Istvan J Enyedy, William J Egan
Jan 8, 2009·Journal of Chemical Information and Modeling·Oliver KorbThomas E Exner
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
May 13, 2009·Journal of Chemical Information and Modeling·Thomas A Halgren
Feb 20, 2010·Nature Reviews. Drug Discovery·Steven M PaulAaron L Schacht
Feb 18, 2011·Journal of Chemical Information and Modeling·Mark McGann
Mar 8, 2011·Drug Discovery Today·Sean EkinsJoel S Freundlich
Nov 1, 2011·Proteins·Wei WangXin Chen
Jan 28, 2012·The AAPS Journal·Tiejun ChengStephen H Bryant
May 10, 2012·Journal of Computer-aided Molecular Design·Russell Spitzer, Ajay N Jain
Aug 2, 2013·Nature Reviews. Drug Discovery·John Arrowsmith, Philip Miller
Apr 9, 2014·Journal of Chemical Information and Modeling·Yan LiRenxiao Wang
Apr 12, 2014·PLoS Computational Biology·Sergio Ruiz-CarmonaS David Morley
May 24, 2014·Journal of Chemical Information and Modeling·Karen T SchomburgMatthias Rarey

❮ Previous
Next ❯

Citations

Oct 27, 2018·Current Drug Targets·Surovi Saikia, Manobjyoti Bordoloi
Apr 10, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bo LiLiang Chen
Jan 9, 2021·Briefings in Bioinformatics·Ali F AlsulamiTom L Blundell
Apr 9, 2021·Journal of Biomolecular Structure & Dynamics·Fábio José Bonfim CardosoFábio Alberto de Molfetta
Jan 18, 2022·Drug Development Research·Jung-Seop LeeSatish Balasaheb Nimse

❮ 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.