Thermodynamic integration

The methods implemented here provide a variety of estimators of conformational free-energies. These are carried out at run-time, or with the use of post-processing tools over the generated output files. The specifics of each estimator are discussed in the documentation of each biasing or analysis method.

A special case is the traditional thermodynamic integration (TI) method, used for example to compute potentials of mean force (PMFs). Most types of restraints (, , , ...) as well as metadynamics () can optionally use TI alongside their own estimator, based on the keywords documented below.

• writeTIPMF $\langle\,$ Write the PMF computed by thermodynamic integration$\,\rangle$
  Context: colvar bias
  Acceptable values: boolean
  Default value: off
  Description: If the bias is applied to a variable that supports the calculation of total forces (see outputotalForce and ), this option allows calculating the corresponding PMF by thermodynamic integration, and writing it to the file outputName.$<$ name$>$ .ti.pmf, where $<$ name$>$ is the name of the bias and the contents of the file are in multicolumn text format (). The total force includes the forces applied to the variable by all bias, except those from this bias itself. If any bias applies time-dependent forces besides the one using this option, an error is raised.

• writeTISamples $\langle\,$ Write the free-energy gradient samples$\,\rangle$
  Context: colvar bias
  Acceptable values: boolean
  Default value: off
  Description: This option allows to compute total forces for use with thermodynamic integration as done by the keyword writeTIPMF. The names of the files containing the variables' histogram and mean thermodynamic forces are outputName.$<$ name$>$ .ti.count and outputName.$<$ name$>$ .ti.force, respectively: these can be used by abf_integrate (see ) or similar utility. Note that because the .force file contains mean forces instead of free-energy gradients, abf_integrate $<$ filename$>$ -s -1.0 should be used. This option is on by default when writeTIPMF is on, but can be enabled separately if the bias is applied to more than one variable, making not possible the direct integration of the PMF at runtime. If any bias applies time-dependent forces besides the one using this option, an error is raised.

In adaptive biasing force (ABF) () the above keywords are not recognized, because their functionality is either included already (conventional ABF) or not available (extended-system ABF).