Theoretical and Computational Challenges in Entropy Evaluation of Macromolecules

Evaluation of entropy is important in biological processes in order to predict the stability of a molecular conformation. The entropy evaluation requires probabilistic modeling of conformations in the internal coordinates. Since fluctuations in the rotational (torsional) angle coordinates make a pivotal contribution to the overall configurational entropy of the molecule, we review circular probability approaches for modeling the torsional angles. Since macromolecules such as proteins have a very large number of interdependent torsional angles and the distributions of many of them could be multimodal and even skewed, we discuss theoretically and computationally challenging problems that arise in the simultaneous modeling of these angles based on data from molecular dynamics simulations.