Rigidity Theory-Based Approximation of Vibrational Entropy Changes upon Binding to Biomolecules.

We introduce a computationally efficient approximation of vibrational entropy changes (ΔS) upon binding to biomolecules based on rigidity theory. From constraint network representations of the binding partners, ΔS is estimated from changes in the number of low frequency ("spongy") modes with respect to changes in the networks' coordination number. Compared to ΔS computed by normal-mode analysis (NMA), our approach yields significant and good to fair correlations for data sets of protein-protein and protein-ligand complexes. Our approach could be a valuable alternative to NMA-based ΔS computation in end-point (free) energy methods.