and residue interaction network (RIN) analyses. To evaluate the influence of single nucleotide polymorphisms (SNPs), they examined four different models: i) wild-type TLR4 (TLR4WT); ii) a double mutant -aspartic acid-to-glycine at position 299 and threonine-to-isoleucine at position 399 (TLR4GI); iii) the aspartic acid-to-glycine mutant (TLR4G299); and iv) the threonine-toisoleucine mutant (TLR4I399). Those mutations were classified as eliminating signalling activity, however, they did not disturb the ligand recognition nor did they establish contact with the associated MD2 protein. Computational studies revealed differences in the dynamic properties of the analysed variants. The authors pointed out that the mutated complexes were less cohesive and displayed both local and global variation in the secondary structure, which could affect the proper exploration of conformational phase space. They also showed that decay in the rotational correlation function together with the observed density distributions and alteration of the number of hydrogen bonds between the protein and ligand could result in the loss of function.