Adaptive sampling is a technique used in computational

molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...

to efficiently simulate

protein folding Protein folding is the physical process by which a protein chain is translated to its native three-dimensional structure, typically a "folded" conformation by which the protein becomes biologically functional. Via an expeditious and reproduci ...

when coupled with molecular dynamics simulations.

Background

Proteins spend a large portion – nearly 96% in some cases – of their

folding Fold, folding or foldable may refer to: Arts, entertainment, and media * ''Fold'' (album), the debut release by Australian rock band Epicure *Fold (poker), in the game of poker, to discard one's hand and forfeit interest in the current pot *Above ...

time "waiting" in various thermodynamic free energy minima. Consequently, a straightforward simulation of this process would spend a great deal of computation to this state, with the transitions between the states – the aspects of protein folding of greater scientific interest – taking place only rarely. Adaptive sampling exploits this property to simulate the protein's

phase space In dynamical system theory, a phase space is a space in which all possible states of a system are represented, with each possible state corresponding to one unique point in the phase space. For mechanical systems, the phase space usually ...

in between these states. Using adaptive sampling, molecular simulations that previously would have taken decades can be performed in a matter of weeks.

Theory

If a protein folds through the

metastable state In chemistry and physics, metastability denotes an intermediate energetic state within a dynamical system other than the system's state of least energy. A ball resting in a hollow on a slope is a simple example of metastability. If the ball i ...

s A -> B -> C, researchers can calculate the length of the transition time between A and C by simulating the A -> B transition and the B -> C transition. The protein may fold through alternative routes which may overlap in part with the A -> B -> C pathway. Decomposing the problem in this manner is efficient because each step can be simulated in parallel.

Applications

Adaptive sampling is used by the Folding@home distributed computing project in combination with Markov state models.

Disadvantages

While adaptive sampling is useful for short simulations, longer trajectories may be more helpful for certain types of biochemical problems.

References

{{reflist , colwidth = 30em , refs = {{cite journal , author = Robert B Best , title = Atomistic molecular simulations of protein folding , journal = Current Opinion in Structural Biology , year = 2012 , type = review , volume = 22 , issue = 1 , pages = 52–61 , doi = 10.1016/j.sbi.2011.12.001 , pmid = 22257762 {{cite web , url=http://folding.stanford.edu/English/FAQ-Simulation , title=Folding@home Simulation FAQ , author1=TJ Lane , author2=Gregory Bowman , author3=Robert McGibbon , author4=Christian Schwantes , author5=Vijay Pande , author6=Bruce Borden , work=Folding@home , publisher=

Stanford University Stanford University, officially Leland Stanford Junior University, is a private research university in Stanford, California. The campus occupies , among the largest in the United States, and enrolls over 17,000 students. Stanford is consider ...

, date=September 10, 2012 , access-date=September 10, 2012 , archive-url=https://web.archive.org/web/20120913150805/http://folding.stanford.edu/English/FAQ-Simulation , archive-date=2012-09-13 , url-status=dead {{cite journal , author1=G. Bowman , author2=V. Volez , author3=V. S. Pande , title = Taming the complexity of protein folding , journal = Current Opinion in Structural Biology , year = 2011 , volume = 21 , issue = 1 , pages = 4–11 , doi = 10.1016/j.sbi.2010.10.006 , pmc = 3042729 , pmid = 21081274 {{cite journal , author = David E. Shaw , author2=Martin M. Deneroff , author3=Ron O. Dror , author4=Jeffrey S. Kuskin , author5=Richard H. Larson , author6=John K. Salmon , author7=Cliff Young , author8=Brannon Batson , author9=Kevin J. Bowers , author10=Jack C. Chao , author11=Michael P. Eastwood , author12=Joseph Gagliardo , author13=J. P. Grossman , author14=C. Richard Ho , author15=Douglas J. Ierardi, Ist , title = Anton, A Special-Purpose Machine for Molecular Dynamics Simulation , journal = Communications of the ACM , volume = 51 , issue = 7 , pages = 91–97 , year = 2008 , doi = 10.1145/1364782.1364802 , doi-access=free {{cite journal , title = Biomolecular Simulation: A Computational Microscope for Molecular Biology , author1=Ron O. Dror , author2=Robert M. Dirks , author3=J.P. Grossman , author4=Huafeng Xu , author5=David E. Shaw , journal =

Annual Review of Biophysics The ''Annual Review of Biophysics'' is a peer-reviewed scientific journal published annually by Annual Reviews. It covers all aspects of biophysics with solicited review articles. Ken A. Dill has been its editor since 2013. According to the ''Jour ...

, year = 2012 , volume = 41 , pages = 429–52 , doi = 10.1146/annurev-biophys-042910-155245 , pmid=22577825 Molecular modelling Simulation software Computational biology Mathematical and theoretical biology Bioinformatics Computational chemistry Hidden Markov models

Background

Theory

Applications

Disadvantages

See also

References