Dear Amir,

You can have two approaches. One is to compute conformational entropy, only internal degrees of freedom,

We have for instance computed the excess entropy of a liquid. The problem lies in the potential you are using. For classical MD only two-body terms are taken into account, but it has been shown for hard potentials that two body terms can account for up to 85% of the total entropy.

You can read into the details:

The supplementary information is open:

http://www.rsc.org/suppdata/c6/cp/c6cp00720a/c6cp00720a1.pdf

The second approach is to rely on statistical thermodynamics, you could compute free energy differences which is a costly mehodology to obtain the adequate convergence:

https://pdfs.semanticscholar.org/1653/115b8d1cc05bf88889dd857f5cd10e74f3ec.pdf

Along with Henao's suggestions, I would like to recommend the "Two-Phase Thermodynamic Model" (2PT). The link of the publication is as follows:

Article Two-Phase Thermodynamic Model for Efficient and Accurate Abs...

In this method, the density of state (DoS) functions (including the normal modes of translation, rotation, and intramolecular vibration motions) are determined from the Fourier transform of the corresponding velocity autocorrelation functions.

Indeed the 2PT model can be usefull in such calculations

Joseph

If your system is not very dense, you can also use Widom's particle insertion method:

http://www.sklogwiki.org/SklogWiki/index.php/Widom_test-particle_method

to obtain the chemical potential and consequently, the free energy of the system. Then you can easily find the absolute entropy.

Entropy: A concept that is not a physical quantity

https://www.researchgate.net/publication/230554936_Entropy_A_concept_that_is_not_a_physical_quantity