Ensemble Biased Metadynamics: a molecular simulation method to sample experimental distributions

Ensemble biased metadynamics (EBMetaD) is a special flavor of metadynamics which allows reproducing one or more probability distributions selected a priori. This is achieved by scaling the Gaussian heights in the metadynamics approach with the inverse of the target distribution.

EBMetaD is available in PLUMED2 and Colvars, for usage please check the respective software manual. In PLUMED2 EBMetaD is referred to as TARGET metadynamics.

The older (deprecated) plumed 1.3 implementation of EBMetaD can be downloaded from this link. Please find below the usage instructions.

This is the sample input file for plumed1.3 that has been used in the application to the T4L protein,

using EPR/DEER experimental distributions as targets (deer_62_109.dat, deer_62_134.dat,

deer_109_134.dat)

PRINT W_STRIDE 250

HILLS RESTART HEIGHT 0.05 W_STRIDE 1000

DISTANCE LIST <g62> <g109> SIGMA 0.5

DISTANCE LIST <g62> <g134> SIGMA 0.5

DISTANCE LIST <g109> <g134> SIGMA 0.5

g62->

991 992

g62<-

g109->

1762 1763

g109<-

g134->

2177 2178

g134<-

PROBRES CV 1 PROBFILE deer_62_109.dat

PROBRES CV 2 PROBFILE deer_62_134.dat

PROBRES CV 3 PROBFILE deer_109_134.dat

LWALL CV 1 LIMIT 21 KAPPA 100

UWALL CV 1 LIMIT 43 KAPPA 100

LWALL CV 2 LIMIT 35 KAPPA 100

UWALL CV 2 LIMIT 47 KAPPA 100

LWALL CV 3 LIMIT 25 KAPPA 100

UWALL CV 3 LIMIT 42 KAPPA 100

ENDMETA

Notes: the target distribution files (deer_62_109.dat, deer_62_134.dat, deer_109_134.dat) contains in the first column the value of the collective variable (e.g. the distance between spin labels) and in the second column the corresponding value of the probability. Note that this probability is automatically normalized by the code, i.e. the input distribution must not be necessarily a normalized probability density.

Border conditions

To reduce systematic errors at the border it is possible to employ the reflection of the Gaussians at the boundaries and removing at the same time the forces beyond the border. An example input on how to do this using the options REFLECTION (to reflect the hills) and INTERVAL (to remove the forces beyond the boundaries) in the current plumed 1.3 implementation is provided below:

PRINT W_STRIDE 250

HILLS RESTART HEIGHT 0.05 W_STRIDE 1000

DISTANCE LIST <g62> <g109> SIGMA 0.5 NOPBC

DISTANCE LIST <g62> <g134> SIGMA 0.5 NOPBC

DISTANCE LIST <g109> <g134> SIGMA 0.5 NOPBC