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Packing defects functionalize soluble proteins
Author(s) -
Fernández Ariel
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.03.002
Subject(s) - nucleophile , deprotonation , proton , catalysis , molecule , chemistry , displacement (psychology) , molecular dynamics , stereochemistry , computational chemistry , biophysics , crystallography , biochemistry , organic chemistry , physics , biology , psychology , quantum mechanics , psychotherapist , ion
This work explores the participation of protein packing defects, the so‐called dehydrons , in biochemical events. We delineate the enabling role of dehydrons as activators of nucleophilic groups. This activation results from the induction of chemical basicity in interfacial water molecules, promoting deprotonation of adjacent nucleophiles. Through multiple steering molecular dynamics with pulling along the proton‐displacement coordinate, we show that nucleophilic groups are functionally enabled by nearby dehydrons that promote proton transference. The computations are validated against experimentally determined pKa decreases at functional sites and biochemical probes of deregulated catalytic activity arising from dehydron‐generating mutations.