Enhanced sampling refers to methods to augment MD simulations by sample the conformational space of proteins more efficiently. In general there are two approaches:
- Adding biases that drive simulations away from or toward certain end states, usually along pre-specified collective variables (e.g., metadynamics). Per Vani et al. (1) this is useful for crossing enthalpic barriers.
- Splitting/stratifying simulations into multiple trajectories (e.g., replica-exchange). Per Vani et al. (1) this is useful for crossing entropic barriers.
1.
Vani BP, Aranganathan A, Wang D, Tiwary P. AlphaFold2-RAVE: From Sequence to Boltzmann Ranking. Journal of Chemical Theory and Computation. 2023;19(14):4351–4. Available from: https://doi.org/10.1021/acs.jctc.3c00290