We study the effect of remote residues in enzyme catalysis by computational predictions and experimental verifications. The big news is that the participation of remote residues in enzyme catalysis is predictable with a simple calculation. Here are some examples:
Figure 1: Variants made of the remote residues predicted by THEMATICS in the enzyme Nitrile Hydratase show significant decrease in catalytic efficiency. [See Heather R. Brodkin, W.R.P. Novak, et al. Biochemistry 50(22), 4923-4935 (2011).]
Figure 2: THEMATICS predicts a single-layered active site for Ketosteroid isomerase and a multilayered active site for PGI. Site-directed mutagenesis and kinetics assays confirm these predictions. [See Srinivas Somarowthu, Heather R. Brodkin, J.A. D'Aquino, Dagmar Ringe, Mary Jo Ondrechen, and Penny J. Beuning, Biochemistry 50(43), 9283-9295 (2011).]