Sampling of rare events using hidden restraints

The Journal of Physical Chemistry. B
Markus ChristenW F van Gunsteren

Abstract

A method to enhance sampling of rare events is presented. It makes use of distance or dihedral-angle restraints to overcome an energy barrier separating two metastable states or to stabilize a transition state between the two metastable states. In order not to perturb these metastable end states themselves, a prefactor is introduced into the restraining energy function, which smoothly increases the weight of this function from zero to one at the transition state or on top of the separating energy barrier and then decreases the weight again to zero at the final state. The method is combined with multi-configurational thermodynamic integration and applied to two biomolecular systems, which were difficult to treat using standard thermodynamic integration. As first example the free energy difference of a cyclic alpha-aminoxy-hexapeptide-ion complex upon changing the ion from Cl- to Na+ was calculated. A large conformational rearrangement of the peptide was necessary to accommodate this change. Stabilizing the transition state by (hidden) restraints facilitates that. As a second example, the free energy difference between the 4C1 and the 1C4 conformation of beta-D-glucopyranoside was calculated. In unrestrained simulations the chang...Continue Reading

References

Dec 5, 1993·Journal of Molecular Biology·R C van SchaikW F van Gunsteren
Jul 27, 2001·Nature·S Fernandez-LopezM R Ghadiri
Oct 30, 2001·The Journal of Organic Chemistry·D YangY D Wu
Apr 25, 2002·Annual Review of Physical Chemistry·Peter G BolhuisPhillip L Geissler
Oct 17, 2002·Journal of the American Chemical Society·Dan YangYun-Dong Wu
Jul 21, 2004·Journal of Computational Chemistry·Chris OostenbrinkWilfred F van Gunsteren

❮ Previous
Next ❯

Citations

Apr 17, 2008·The Journal of Chemical Physics·Jozef Hritz, Chris Oostenbrink
Nov 30, 2006·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Daniel TrzesniakWilfred F van Gunsteren
Nov 18, 2015·Journal of Chemical Theory and Computation·Oliwia M SzklarczykWilfred F van Gunsteren
Jun 16, 2007·Journal of Computational Chemistry·Markus Christen, Wilfred F van Gunsteren
Dec 4, 2012·Angewandte Chemie·Wilfred F van Gunsteren
Jun 20, 2007·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Markus ChristenWilfred F van Gunsteren
Jul 15, 2015·Journal of Computational Chemistry·Noah S Bieler, Philippe H Hünenberger
Jan 17, 2020·The Journal of Chemical Physics·Maria Pechlaner, Wilfred F van Gunsteren
Apr 13, 2011·Journal of Computational Chemistry·Stephanie B A De BeerChris Oostenbrink
Mar 26, 2013·Journal of Computational Chemistry·Jose Antonio Garate, Chris Oostenbrink
Jan 13, 2009·Journal of Chemical Theory and Computation·Juan TorrasAdrian E Roitberg
Sep 3, 2009·The Journal of Physical Chemistry. B·Jozef Hritz, Chris Oostenbrink
Jul 8, 2014·Journal of Chemical Theory and Computation·Niels Hansen, Wilfred F van Gunsteren
May 2, 2014·The Journal of Physical Chemistry. B·Joseph W KausJ Andrew McCammon
Sep 13, 2017·Journal of Chemical Theory and Computation·Jan Walther Perthold, Chris Oostenbrink
Nov 2, 2011·The Journal of Physical Chemistry. B·Sereina RinikerWilfred F van Gunsteren
Nov 18, 2015·Journal of Chemical Theory and Computation·Noah S BielerPhilippe H Hünenberger
Feb 12, 2013·Journal of Chemical Theory and Computation·Anita de Ruiter, Chris Oostenbrink

❮ Previous
Next ❯

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.