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

We introduce a computationally efficient approximation of vibrational entropy changes (ΔS_vib) upon binding to biomolecules based on rigidity theory. From constraint network representations of the binding partners, ΔS_vib is estimated from changes in the number of low frequency ("spongy") modes with respect to changes in the networks' coordination number. Compared to ΔS_vib 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_vib computation in end-point (free) energy methods.