Dielectric relaxation of water: assessing the impact of localized modes, translational diffusion, and collective dynamics

2021 ◽  
Vol 23 (37) ◽  
pp. 20875-20882
Author(s):  
Christoph Hölzl ◽  
Harald Forbert ◽  
Dominik Marx
Keyword(s):  
Molecular Dynamics ◽  
Ab Initio ◽  
Dielectric Relaxation ◽  
Molecular Dynamics Simulations ◽  
Relaxation Spectrum ◽  
Translational Diffusion ◽  
Localized Modes ◽  
Collective Dynamics ◽  
Dynamics Simulations ◽  
The Impact

The dielectric relaxation spectrum of water can be quantitatively reproduced by ab initio molecular dynamics simulations. Its decomposition into auto- and crosscorrelation terms suggests that fits of experimental spectra may require revision.

scholarly journals Exploiting correlated molecular-dynamics networks to counteract enzyme activity–stability trade-off

2018 ◽  
Vol 115 (52) ◽  
pp. E12192-E12200 ◽  
Author(s):  
Haoran Yu ◽  
Paul A. Dalby
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Active Site ◽  
Dynamic Networks ◽  
Aromatic Aldehydes ◽  
Active Site Residues ◽  
Trade Off ◽  
Highly Correlated ◽  
Dynamics Simulations ◽  
The Impact

The directed evolution of enzymes for improved activity or substrate specificity commonly leads to a trade-off in stability. We have identified an activity–stability trade-off and a loss in unfolding cooperativity for a variant (3M) of Escherichia coli transketolase (TK) engineered to accept aromatic substrates. Molecular dynamics simulations of 3M revealed increased flexibility in several interconnected active-site regions that also form part of the dimer interface. Mutating the newly flexible active-site residues to regain stability risked losing the new activity. We hypothesized that stabilizing mutations could be targeted to residues outside of the active site, whose dynamics were correlated with the newly flexible active-site residues. We previously stabilized WT TK by targeting mutations to highly flexible regions. These regions were much less flexible in 3M and would not have been selected a priori as targets using the same strategy based on flexibility alone. However, their dynamics were highly correlated with the newly flexible active-site regions of 3M. Introducing the previous mutations into 3M reestablished the WT level of stability and unfolding cooperativity, giving a 10.8-fold improved half-life at 55 °C, and increased midpoint and aggregation onset temperatures by 3 °C and 4.3 °C, respectively. Even the activity toward aromatic aldehydes increased up to threefold. Molecular dynamics simulations confirmed that the mutations rigidified the active-site via the correlated network. This work provides insights into the impact of rigidifying mutations within highly correlated dynamic networks that could also be useful for developing improved computational protein engineering strategies.

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