2016
DOI: 10.1002/prot.25213
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Microscopic mechanisms that govern the titration response and p K a values of buried residues in staphylococcal nuclease mutants

Abstract: To probe the microscopic mechanisms that govern the titration behavior of buried ionizable groups, microsecond explicit solvent molecular dynamics simulations are carried out for several mutants of Staphylococcal nuclease using both fixed charge and polarizable force fields. While the ionization of Asp 66, Glu 66, and Lys 125 lead to enhanced structural fluctuations and partial unfolding of adjacent α-helical regions, the ionization of Lys 25 causes local unfolding of adjacent β sheets. Using the sampled confo… Show more

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Cited by 34 publications
(37 citation statements)
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“…Charge-changing mutations, whether buried or surface-exposed, can alter protein charge, electrostatics, and conformation [16]. Electrostatics of surface residues have been shown to play a key role in protein-protein interactions [17], protein-membrane interactions [18, 19], and kinase substrate recognition [20].…”
Section: Discussionmentioning
confidence: 99%
“…Charge-changing mutations, whether buried or surface-exposed, can alter protein charge, electrostatics, and conformation [16]. Electrostatics of surface residues have been shown to play a key role in protein-protein interactions [17], protein-membrane interactions [18, 19], and kinase substrate recognition [20].…”
Section: Discussionmentioning
confidence: 99%
“…A current work-around to the fixed backbone is to average the charge state distributions calculated in multiple snapshots from MD simulation or from multiple crystal structures, which provide a distribution of likely conformations. One problem is that an MD simulation will always seek to stabilize the charge states assigned to the simulation [73,74].…”
Section: Methods Of Calculationmentioning
confidence: 99%
“…Calculations of the p K a of protein residues are highly dependent on the conformation of the protein and the description of the solvent . Starting from the X‐Ray structure, Thioredoxin was simulated in explicit solvent for 2 μ s with Asp26 in the protonated (state A) or deprotonated form (state B).…”
Section: Resultsmentioning
confidence: 99%
“…Calculations of the pK a of protein residues are highly dependent on the conformation of the protein and the description of the solvent. 10,39,42 Starting from the X-Ray structure, Thioredoxin was simulated in explicit solvent for 2 μs with Asp26 in the protonated (state A) or deprotonated form (state B). Slow conformational transitions related to changes in the position of backbone atoms were monitored by principal component analysis based on the backbone RMSD.…”
Section: Conformational Analysis Of Thioredoxinmentioning
confidence: 99%
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