| Simulated annealing |
System is heated and then gradually cooled. May involve multiple iterations to sample different minima on the free energy landscape. One of the oldest techniques, but recently shown to increase sampling by at least an order of magnitude. Does not sample from a Boltzmann distribution. |
[107,108] |
| Simulated tempering |
Like simulated annealing, but samples from a Boltzmann distribution. |
[109,110] |
| T-REMD: Temperature replica exchange MD |
Multiple independent replicas in parallel, with coordinates exchanged at regular intervals. Sensitive to the choice of control parameters; substantial literature regarding their optimisation. |
[86,91,111–117] |
| R-REMD: Reservoir REMD |
T-REMD with the highest temperature replica replaced with a pre-generated reservoir of structures. Dependent on reservoir adequately covering conformational space. |
[118–121] |
| M-REMD: Multiplexed REMD |
T-REMD with several independent simulations at each temperature. Exchanges can occur between these and between temperatures. Takes advantage of highly parallel computing. |
[122] |
| TAMD: Temperature-accelerated MD |
Explores free-energy landscape of a large set of CVs at the physical temperature using an artificially high fictitious temperature. |
[123] |
| REST and REST2: Replica exchange with solute tempering |
Only the temperature of the solute differs between replicas. Increases the probability of exchanges by reducing the effective system size compared at each exchange attempt. |
[91,124] |
| SGLD: Self-guided Langevin dynamics |
SGLD increases the temperature of low-frequency motions only, with the SGLD temperatures scaled across replicas. The implementation of Wu et al. uses the SGLD partition function to remove the problems caused by the ad hoc force term of Lee and Olson [125]. |
[125,126] |
