Enhanced Sampling I: Free Energy Methods
Go beyond a single trajectory - compute real free energy profiles with umbrella sampling, WHAM, and replica exchange.
About this course
A hands-on follow-on to Introduction to Molecular Dynamics, focused entirely on the enhanced sampling techniques real research relies on whenever a question can't be answered by a single unbiased trajectory. Using alanine dipeptide as a fast, well-characterized model system, you'll run umbrella sampling windows and reconstruct a potential of mean force with WHAM, then run temperature replica exchange and compare what each method reveals about the same conformational landscape.
Who it's for
Graduates of Introduction to Molecular Dynamics (or anyone who passes its qualifying exam) who want to move beyond straightforward production MD into quantitative free energy calculations - the kind of analysis real structural biology and drug discovery research depends on.
Prerequisites
Requires Introduction to Molecular Dynamics with GROMACS and CHARMM-GUI - OR solid prior background and hands-on practical experience with MD simulation using GROMACS, proven by scoring at least 85% on the qualifying exam.
Either of the following qualifies you:
- Completed Introduction to Molecular Dynamics with GROMACS and CHARMM-GUI
- Or: solid prior background and hands-on experience with MD simulation using GROMACS, proven by scoring at least 85% on the qualifying exam
Learning outcomes
By the end of this course you will be able to define and justify a reaction coordinate, set up and run umbrella sampling windows with the GROMACS pull code, reconstruct a free energy profile with WHAM including statistical uncertainty, run a temperature replica exchange simulation, and explain when each method is the right tool for a given problem.
Weekly structure
Free Energy Landscapes and Reaction Coordinates
Why some questions can't be answered by a single MD trajectory, what a reaction coordinate is, and building the alanine dipeptide system you'll use all course.
Umbrella Sampling and WHAM
Biasing a system to sample rare conformations on purpose, then mathematically removing that bias to recover the true free energy profile.
Replica Exchange Molecular Dynamics
A second, fundamentally different enhanced sampling strategy - running coupled replicas at different temperatures - and when to reach for it instead of umbrella sampling.
- Duration
- 3 weeks
- Commitment
- Approximately 5–7 hours per week, including one scheduled live laboratory session.
- Certificate
- Included
- Cost
- Free
Cohorts
No cohort has been scheduled yet.
No cohort is open for applications right now.