# Alchemical free energy calculations

**URL:** https://ask.bioexcel.eu/t/alchemical-free-energy-calculations/3102
**Category:** pmx
**Created:** [June 11, 2021, 9:11am UTC](https://ask.bioexcel.eu/t/alchemical-free-energy-calculations/3102 "2021-06-11T09:11:39Z")
**Posts on this page:** 2
**Page:** 1

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### Author: ![isilayozturk](https://dub1.discourse-cdn.com/flex013/user_avatar/ask.bioexcel.eu/isilayozturk/32/451_2.png) [@isilayozturk](https://ask.bioexcel.eu/u/isilayozturk)
#### Post date: [June 11, 2021, 9:11am UTC](https://ask.bioexcel.eu/t/alchemical-free-energy-calculations/3102/1 "2021-06-11T09:11:39Z")

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what is the main difference alchemical free energy calculations and umbrella or metadynamics ?

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### Author: ![vgapsys](https://avatars.discourse-cdn.com/v4/letter/v/7993a0/32.png) [@vgapsys](https://ask.bioexcel.eu/u/vgapsys)
#### Post date: [October 1, 2021, 9:55am UTC](https://ask.bioexcel.eu/t/alchemical-free-energy-calculations/3102/2 "2021-10-01T09:55:19Z")

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Alchemical free energy calculations use non-physical, i.e. alchemical, pathways to estimate free energy differences between the physical end states. Umbrella sampling or metadynamics bias the simulations to enhance sampling along the chosen reaction coordinate to eventually recover free energy landscape along this coordinate.