Tryptophan Conformations Associated with Partial Unfolding in Ribonuclease T1 |
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Authors: | Samuel L.C. Moors Abel Jonckheer Marc De Maeyer Arnout Ceulemans |
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Affiliation: | † Laboratory of Quantum Chemistry and INPAC Institute for Nanoscale Physics and Chemistry, Katholieke Universiteit Leuven, Leuven, Belgium ‡ Laboratory for Bio-Molecular Dynamics, Katholieke Universiteit Leuven, Leuven, Belgium § Laboratory for Bio-Molecular Modelling and BioMacS, Katholieke Universiteit Leuven, Leuven, Belgium |
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Abstract: | The origin of the biexponential fluorescence decay of Trp in ribonuclease T1 under mildly destabilizing conditions, such as increased pH or temperature, or the presence of detergent, is still not understood. We have performed two extended replica-exchange molecular dynamics simulations to obtain a detailed representation of the native state at two protonation states corresponding to a high and low pH. At high pH, the appearance of partially unfolded states is evident. We found that this pH-induced destabilization originates from increased global repulsion as well as reduced local favorable electrostatic interactions and reduced H-bonding strength of His27, His40, and His92. At high pH, alternative tryptophan rotamers appear and are linked to a distorted environment of the tryptophan, which also acts as a separate source of ground-state heterogeneity. The total population of these alternative conformations agrees well with the amplitude of the experimentally observed secondary fluorescence lifetime. |
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