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Soft–Soft interactions in the protein–protein recognition process: The K + channel‐charybdotoxin case
Author(s) -
Aparicio Felipe,
GonzálezRivas Nelly,
Ireta Joel,
Rojo Arturo,
Escobar Laura I.,
Cedillo Andrés,
Galván Marcelo
Publication year - 2012
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.24278
Subject(s) - charybdotoxin , chemistry , reactivity (psychology) , potassium channel , substituent , ion channel , mutant , stereochemistry , biophysics , computational chemistry , potassium , receptor , biochemistry , organic chemistry , medicine , alternative medicine , pathology , gene , biology
Abstract Molecular recognition between peptide blockers and ionic channels is a complex process that involves many effects. To determine if the short‐range charge transfer effects play a significant role in this interaction, a chemical reactivity analysis of charybdotoxin (ChTX) and six of its mutants was carried out using global and local reactivity indices. The results show that global softness correlates with the affinity of ChTX, and its mutants to the channel indicating that soft–soft interactions play a role in the recognition process between ChTX and a potassium channel. The analysis of the local reactivity indicates that the toxin as a whole can be seen as a complex polydentate ligand with several places to coordinate with the external vestibule of the pore of the potassium channels. The successful treatment of point mutations supports the idea of using this tool in the study of chemical reactivity in proteins, in a similar way as substituent effects in organic chemistry. © 2012 Wiley Periodicals, Inc.