Enhanced molecular dynamics sampling of drug target conformations

Biopolymers
Isela G Rodriguez-BusseyDonald Hamelberg

Abstract

Computational docking and virtual screening are two main important methods employed in structure-based drug design. Unlike the traditional approach that allows docking of a flexible ligand against a handful of receptor structures, receptor flexibility has now been appreciated and increasingly incorporated in computer-aided docking. Using a diverse set of receptor conformations increases the chances of finding potential drugs and inhibitors. Molecular dynamics (MD) is greatly useful to generate various receptor conformations. However, the diversity of the structures of the receptor, which is usually much larger than the ligand, depends on the sampling efficiency of MD. Enhanced sampling methods based on accelerated molecular dynamics (aMD) can alleviate the sampling limitation of conventional MD and aid in representation of the phase space to a much greater extent. RaMD-db, a variant of aMD that applies boost potential to the rotatable dihedrals and non-bonded diffusive degrees of freedom has been proven to reproduce the equilibrium properties more accurately and efficiently than aMD. Here, we discuss recent advances in the aMD methodology and review the applicability of RaMD-db as an enhanced sampling method. RaMD-db is shown t...Continue Reading

References

Dec 1, 1994·Journal of Computer-aided Molecular Design·T HuberW F van Gunsteren
Sep 1, 1995·Physical Review. E, Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics·H Grubmüller
Jan 13, 2000·International Journal of Experimental Pathology·L AndreevaC J Green
Aug 23, 2000·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·G Klebe
Apr 4, 2002·Proceedings of the National Academy of Sciences of the United States of America·Daryl A BoscoDorothee Kern
Apr 12, 2002·The Journal of Biological Chemistry·Vyacheslav YurchenkoMichael Bukrinsky
Sep 25, 2002·Proceedings of the National Academy of Sciences of the United States of America·Alessandro Laio, Michele Parrinello
Dec 12, 2002·Biochemistry·William J WedemeyerHarold A Scheraga
Jun 18, 2003·The Journal of General Virology·Santanu BoseAmiya K Banerjee
Jun 27, 2003·Journal of Medicinal Chemistry·Susan L McGovern, Brian K Shoichet
Mar 19, 2004·Journal of Medicinal Chemistry·Richard A FriesnerPeter S Shenkin
Mar 19, 2004·Journal of Medicinal Chemistry·Thomas A HalgrenJay L Banks
Jul 23, 2004·The Journal of Chemical Physics·Donald HamelbergJ Andrew McCammon
Sep 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Pu LiuB J Berne
Oct 6, 2005·Journal of the American Chemical Society·Donald Hamelberg, J Andrew McCammon
Oct 14, 2005·Journal of Medicinal Chemistry·Ian L AlbertsPhilip M Dean
Sep 29, 2006·Journal of Medicinal Chemistry·Andrew R LeachCatherine E Peishoff
Mar 23, 2007·Journal of the American Chemical Society·Phineus R L MarkwickMartin Blackledge
Aug 19, 2007·Current Protein & Peptide Science·Romano T Kroemer
Feb 20, 2008·The Journal of Chemical Physics·Yi Qin Gao
Jul 24, 2008·The Journal of Chemical Physics·Tongye Shen, Donald Hamelberg
Jan 9, 2009·Journal of the American Chemical Society·Donald Hamelberg, J Andrew McCammon
Apr 22, 2009·The Journal of Biological Chemistry·Udayan ChatterjiPhilippe Gallay
Jun 2, 2009·Biochemistry·Sebastian DaumCordelia Schiene-Fischer
Nov 19, 2009·Journal of the American Chemical Society·Phineus R L MarkwickMartin Blackledge
Jan 13, 2010·Journal of the American Chemical Society·Phineus R L MarkwickJ Andrew McCammon
Jun 15, 2010·Trends in Biochemical Sciences·Peter CsermelyRuth Nussinov
Nov 13, 2010·Journal of Chemical Theory and Computation·Jeff Wereszczynski, J Andrew McCammon
Jan 5, 2011·Journal of Chemical Information and Modeling·Somisetti V Sambasivarao, Orlando Acevedo
Feb 12, 2011·The Journal of International Medical Research·J Lee, S S Kim
Apr 19, 2011·Current Opinion in Pharmacology·Martin TheuerkornCordelia Schiene-Fischer
May 3, 2011·PLoS Computational Biology·Denis BucherJ Andrew McCammon
Oct 22, 2011·Physical Chemistry Chemical Physics : PCCP·Phineus R L Markwick, J Andrew McCammon
Nov 1, 2011·BMC Biology·Jacob D Durrant, J Andrew McCammon
Mar 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Urmi DoshiDonald Hamelberg
May 2, 2012·Molecular and Biochemical Parasitology·Alejandro Marín-MenéndezAngus Bell
Dec 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Wei ZhuEric Oldfield
Jan 15, 2013·Journal of Chemical Information and Modeling·Mulpuri NagarajuDonald Hamelberg
Aug 12, 2014·European Journal of Medicinal Chemistry·Hongtao Zhao, Amedeo Caflisch
Jan 15, 2015·Biochimica Et Biophysica Acta·Safieh Tork LadaniDonald Hamelberg
Apr 3, 2014·The Journal of Physical Chemistry Letters·Urmi Doshi, Donald Hamelberg
Nov 6, 2015·Quarterly Reviews of Biophysics·Kalli KappelJ Andrew McCammon

❮ Previous
Next ❯

Citations

Nov 1, 2016·Journal of Chemical Theory and Computation·Nathan A BernhardtUlrich H E Hansmann
Feb 7, 2017·Expert Opinion on Drug Discovery·Aravindhan Ganesan, Khaled Barakat
Feb 10, 2017·The Journal of Physical Chemistry. B·Beytullah OzgurOzlem Keskin
Feb 9, 2017·Proteins·Govardhan A BalajiShashidhar N Rao
Sep 12, 2017·Advanced Healthcare Materials·Cecilia SahlgrenNiklas Sandler
Jun 2, 2018·The Journal of Physical Chemistry. B·Isela Rodriguez-BusseyDonald Hamelberg

❮ 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.