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is another free-energy calculation technique that is typically used for calculating the free-energy change associated with a change in "position" coordinates as opposed to "chemical" coordinates, although umbrella sampling can also be used for a chemical transformation when the "chemical" coordinate
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Free-energy perturbation calculations only converge properly when the difference between the two states is small enough; therefore it is usually necessary to divide a perturbation into a series of smaller "windows", which are computed independently. Since there is no need for constant communication
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252:{\displaystyle \Delta F(\mathbf {A} \to \mathbf {B} )=F_{\mathbf {B} }-F_{\mathbf {A} }=-k_{\text{B}}T\ln \left\langle \exp \left(-{\frac {E_{\text{B}}-E_{\mathbf {A} }}{k_{\text{B}}T}}\right)\right\rangle _{\mathbf {A} },}
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is treated as a dynamic variable (as in the case of the Lambda dynamics approach of Kong and Brooks). An alternative to free-energy perturbation for computing potentials of mean force in chemical space is
605:
Sampson, Jared M.; Cannon, Daniel A.; Duan, Jianxin; Epstein, Jordan C. K.; Sergeeva, Alina P.; Katsamba, Phinikoula S.; Mannepalli, Seetha M.; Bahna, Fabiana A.; Adihou, Hélène (2024-04-24),
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Sampson, Jared M.; Cannon, Daniel A.; Duan, Jianxin; Epstein, Jordan C. K.; Sergeeva, Alina P.; Katsamba, Phinikoula S.; Mannepalli, Seetha M.; Bahna, Fabiana A.; Adihou, Hélène (2024-04-24),
319:
between the simulation for one window and the next, the process can be trivially parallelized by running each window on a different CPU, in what is known as an "
60:
The FEP method was introduced by Robert W. Zwanzig in 1954. According to the free-energy perturbation method, the free-energy difference for going from state
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obtained is for "mutating" one molecule onto another, or it may be a difference of geometry, in which case one obtains a free-energy map along one or more
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Several software packages have been developed to help perform FEP calculations. Below is a short list of some of the most common programs:
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used for FEP simulations cannot handle breaking bonds. A hybrid method that has the advantages of both QM and MM calculations is called
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Robust prediction of relative binding energies for protein-protein complex mutations using free energy perturbation calculations
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Robust prediction of relative binding energies for protein-protein complex mutations using free energy perturbation calculations
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method. Adaptations to FEP exist which attempt to apportion free-energy changes to subsections of the chemical structure.
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studies and antibody affinity maturation. For the study of reactions it is often necessary to involve a
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554:, Methods in Molecular Biology, vol. 2266, New York, NY: Springer US, pp. 203–226,
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Jespers, Willem; Åqvist, Johan; Gutiérrez-de-Terán, Hugo (2021), Ballante, Flavio (ed.),
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FEP calculations have been used for studying host–guest binding energetics,
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on reactions, and enzymatic reactions. Other applications are the
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Irwin, B. W. J., J. Chem. Theory Comput. 2018, 14, 6, 3218–3227.
548:"Free Energy Calculations for Protein–Ligand Binding Prediction"
438:
381:. Another alternative, which is probably more efficient, is the
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358:(QM) representation of the reaction center because the
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may be in the atom types involved, in which case the Δ
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is obtained from the following equation, known as the
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488:Zwanzig, R. W. J. Chem. Phys. 1954, 22, 1420–1426.
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293:is also computed. The difference between states
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552:Protein-Ligand Interactions and Drug Design
309:. This free-energy map is also known as a
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740:: CS1 maint: archived copy as title (
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699:"The Amber Molecular Dynamics Package"
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27:Method in computational chemistry
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560:10.1007/978-1-0716-1209-5_12
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663:"Flare FEP | Cresset"
681:"FEP+ | Schrödinger"
617:10.1101/2024.04.22.590325
518:10.1101/2024.04.22.590325
466:Thermodynamic integration
379:thermodynamic integration
650:10.1021/acs.jctc.8b00027
383:Bennett acceptance ratio
31:Free-energy perturbation
18:Free energy perturbation
779:Computational chemistry
321:embarrassingly parallel
312:potential of mean force
43:computational chemistry
37:) is a method based on
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55:Metropolis Monte Carlo
784:Statistical mechanics
667:www.cresset-group.com
254:
39:statistical mechanics
307:reaction coordinates
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685:www.schrodinger.com
360:molecular mechanics
356:quantum-mechanical
279:Boltzmann constant
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51:molecular dynamics
760:www.qsimulate.com
569:978-1-0716-1209-5
494:10.1063/1.1740409
471:Umbrella sampling
374:Umbrella sampling
341:virtual screening
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49:differences from
16:(Redirected from
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45:for computing
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723:on 2014-12-28
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57:simulations.
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725:. Retrieved
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364:force fields
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756:"QSimulate"
703:ambermd.org
352:mutagenesis
327:Application
268:temperature
47:free-energy
773:Categories
727:2015-01-18
632:2024-05-04
591:2021-03-30
533:2024-05-04
477:References
429:MacroModel
586:226701336
397:Flare FEP
349:in silico
323:" setup.
196:−
180:−
172:
160:
141:−
123:−
97:→
83:Δ
64:to state
736:cite web
626:11071377
578:33759129
527:11071377
460:See also
389:Software
235:⟩
165:⟨
434:MOLARIS
424:GROMACS
419:Desmond
315:(PMF).
277:is the
266:is the
623:
584:
576:
566:
524:
444:Tinker
414:CHARMM
262:where
582:S2CID
454:QUELO
404:AMBER
368:QM/MM
362:(MM)
742:link
574:PMID
564:ISBN
439:NAMD
409:BOSS
400:FEP+
297:and
646:doi
621:PMC
613:doi
556:doi
522:PMC
514:doi
490:doi
333:pKa
169:exp
53:or
35:FEP
775::
758:.
738:}}
734:{{
701:.
683:.
665:.
619:,
611:,
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370:.
347:,
270:,
157:ln
72::
762:.
744:)
730:.
705:.
687:.
669:.
652:.
648::
615::
595:.
558::
516::
496:.
492::
449:Q
303:F
299:B
295:A
291:B
287:A
283:A
275:B
272:k
264:T
247:,
241:A
230:)
223:T
218:B
214:k
205:A
200:E
191:B
187:E
176:(
154:T
149:B
145:k
138:=
132:A
127:F
117:B
112:F
108:=
105:)
101:B
93:A
89:(
86:F
66:B
62:A
33:(
20:)
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