Significant progress has been made in the past fifty years in computing the entropy of soft matter and molecular systems (1-4). This especially relates to biomolecular systems which are central to efforts in drug discovery, biotechnology and understanding life itself. The earliest methods to calculate the absolute conformational entropy of complex molecules such as proteins were normal mode analysis (5,6) and quasi-harmonic analysis (7,8). Both approaches make the severe approximation that the molecule is restricted to a single basin of the potential energy surface, which is approximated by a multidimensional harmonic oscillator. Normal mode analysis derives the associated force constants from the Hessian matrix (5,6). Quasi-harmonic analysis derives force constants from the variance-covariance matrix of the displacements measured in constant temperature molecular dynamics simulations (7,8). Both methods fail if the system is inherently anharmonic or if non-linear correlations exist between atomic motions. This is now known to be the rule rather than the exception for biomolecules, many of which are highly disordered. Moreover, neither method can account for the entropy contributions of the surrounding solvent and ions and so such terms were (9,10) and still are (11) commonly treated using continuum and empirical terms.

A number of computational methods have been proposed to address these inadequacies to much more accurately compute the entropy of biomolecular systems (1-4,). This also includes progress in experimental methods based on NMR (12). On the computational front, recent methodological developments account for the solvent contribution, the large number of conformational states of polymeric molecules, the anharmonic nature of these states, non-linear correlated motions between them, and the multiple length scales (13-24). Advances are represented by the number of new software packages that have been released to enable widespread usage of the new entropy methods. Methods to calculate solvent entropy include inhomogeneous solvation theory in WaterMap (13) and grid-version SSTMAP (14), the 2PT method based on velocity-autocorrelation functions (15), and a mutual information method with permutation reduction in Per|Mut (16). Methods to calculate biomolecular entropy include the mutual information expansion method (17) implemented in ENTROPICAL (18) and PARENT (19) and including a multibody local approximation in CENCALC (20), the nearest-neighbour method in PDB2ENTROPY (21), the multiscale cell correlation method in CodeEntropy (22) which has the advantage of being also applicable to liquids (23)  and the mining minima method VM2 (24). The accuracy, generality, practicality and utility of all these these approaches is still being worked out.

Despite the fundamental nature of entropy, few scientific meetings have been dedicated to its determination and its role in soft matter and biomolecular systems. Most meetings have focused on differences in free energy which are unable to connect thermodynamics with structure and explain the value of the entropy over the whole system. By bringing together theorists, computational scientists and experimentalists, the proposed workshop “Entropy in Soft Matter Systems” aims to play a transformative and catalytic role in delineating the main challenges in the field, enabling crosstalk across the theory-experiment divide and stimulating active collaborations to drive the field forward.