What is the main difference between surface- and interior-critical residues?
Allosteric surface residues play regulatory roles that are fundamentally distinct from those of allosteric residues within the interior. While surface residues may often constitute the sources or sinks of allosteric signals, interior residues act to transmit such signals. Thus, different approaches are needed for identifying these two classes of residues. Surface-critical residues are identified by finding pockets such that the occlusion of such pockets is likely to interfere with large-scale protein motions (see Documentation for details; see also Ming and Wall, 2005; Mitternacht and Berezovsky, 2011). Interior-critical residues are identified by finding information-flow bottlenecks within the protein structure (see Documentation and main paper for details and Sethi et al, 2009).
Ming, Dengming, and Michael E. Wall. “Quantifying allosteric effects in proteins.” Proteins: Structure, Function, and Bioinformatics 59.4 (2005): 697-707.
Mitternacht, S. and Berezovsky, I.N. (2011). Binding leverage as a molecular basis for allosteric regulation. PLoS Comput. Biol. 7, e1002148.
Sethi, A., Eargle, J., Black, A.A., and Luthey-Schulten, Z. (2009). Dynamical networks in tRNA:protein complexes. Proc. Natl. Acad. Sci. U. S. A. 106, 6620–5.