Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.2.1.17 (
lysozyme
)
21,489
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The ionization state of titratable amino acids strongly affects proteins structure and functioning in a large number of biological processes. It is therefore essential to be able to characterize the p
K
a
of ionizable groups inside proteins and to understand its microscopic determinants in order to gain insights into many functional properties of proteins. A big effort has been devoted to the development of theoretical approaches for the prediction of deprotonation free energies, yet the accurate theoretical/computational calculation of p
K
a
values is recognized as a current challenge. A methodology based on a hybrid quantum/classical approach is here proposed for the computation of deprotonation free energies. The method is applied to calculate the p
K
a
of
formic acid
, methylammonium, and methanethiol, providing results in good agreement with the corresponding experimental estimates. The p
K
a
is also calculated for aspartic acid and lysine as single residues in solution and for three aspartic/glutamic acids inside a well-characterized protein: hen egg white
lysozyme
. While for small molecules the method is able to deal with multiple protonation states of all titratable groups, this becomes computationally very expensive for proteins. The calculated p
K
a
values for the single amino acids (except for the zwitterionic aspartic acid) and inside the protein display a systematic shift with respect to the experimental values that suggests that the fine balance between hydrophobic and polar interactions might be not accurately reproduced by the usual classical force-fields, thus affecting the computation of deprotonation free energies. The calculated p
K
a
shifts inside the protein are in good agreement with the corresponding experimental ones (within 1 p
K
a
unit), well reproducing the p
K
a
changes due to the protein environment even in the case of large p
K
a
shifts.
...
PMID:Fully Atomistic Multiscale Approach for p
K
a
Prediction. 3242 81
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