The binding free energies (ΔG) in kcal/mol at the five interfaces computed by both molecular mechanics generalized Born surface area (MM-GBSA) and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methods.

These interfaces are TLR4/MD2 (and its symmetry-related image TLR4*/MD2*), TLR4/TLR4*, and TLR4/MD2* (and its symmetry-related images TLR4*/MD2). The free energies in each of the ligand-free TLR4-MD2 heterodimer, (TLR4-MD2)2 tetramer, lipopolysaccharide (LPS)-bound (TLR4-MD2)2 tetramer, and neoseptin3-bound (TLR4-MD2)2 tetramer complexes are averaged over the average of their 4 different trajectories consisting of overall 4000 frames. A negative value is a favorable free energy, while a positive value is an unfavorable. The values in parenthesis are standard deviation. ΔEMM is molecular mechanics free energy which is divided into ΔEele and ΔEvdw representing the contributions from the electrostatic and van der Waals interactions, respectively. ΔGsol is solvation free energy expressed by ΔGpol and ΔGnonpol, the polar and non-polar contributions, respectively.