The hypothetical scanning molecular dynamics (HSMD) method enables
one to calculate the * absolute* entropy

Notice, however, that in most applications we are interested in
the free energy difference Δ*F*_{mn} (and Δ*S*_{mn})
between two states *m* and *n* (e.g., a helical and hairpin
states of a peptide); such states are called in our papers
“microstates”.

The software presented here is related only to the HSMD part of
the entire method (HSMD-TI). To understand this part let’s assume a
peptide in a box of explicit water (e.g., TIP3P) simulated by MD
(e.g., using the software AMBER); we wish to calculate the
contribution of the peptide to *S*. The method works as follows:

**(a)** From the above (initial) MD trajectory a sample of *n*
equally spaced snapshots of the entire system are selected.

**(b)** For each snapshot *i *the conformation of the
peptide should be “reconstructed” step-by-step by calculating
transition probabilities (TPs) where their product leads to an
approximation, *P*_{i} for the Boltzmann
probability density of peptide’s conformation in *i*. This
reconstruction is done in two stages:

Stage 1 is carried out again within AMBER. The data produced in
stage 1 are stored on files which are read in stage 2 by the software
provided here (this software consists of two programs,
RECONSTR_angles_list_amber.c and RECONSTR_count_amber.c described
later, which for brevity we denote as the **program**).
This **program** calculates the TPs, their product, *P*_{i}
and the entropy *S*^{A}
=-*k*_{B}*T*ln*P*_{i} related
* only *to the peptide conformation of

The advantage of this two-stage procedure is that the raw data of the time consuming stage 1 is calculated only once and can be analyzed (typically) many times in stage 2 for different HSMD parameters. Also, the initial MD trajectory and the simulations of stage 1 can be carried out by any of the standard software packages – TINKER, CHARMM, etc., as well as AMBER discussed here.

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