Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa’s of proteins as a function of pH. Test on a large set of proteins. / Vorobjev, Yury N.; Scheraga, Harold A.; Vila, Jorge A.
в: Journal of Biomolecular Structure and Dynamics, Том 36, № 3, 17.02.2018, стр. 561-574.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa’s of proteins as a function of pH. Test on a large set of proteins
AU - Vorobjev, Yury N.
AU - Scheraga, Harold A.
AU - Vila, Jorge A.
N1 - Publisher Copyright: © 2017 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2018/2/17
Y1 - 2018/2/17
N2 - A computational method, to predict the pKa values of the ionizable residues Asp, Glu, His, Tyr, and Lys of proteins, is presented here. Calculation of the electrostatic free-energy of the proteins is based on an efficient version of a continuum dielectric electrostatic model. The conformational flexibility of the protein is taken into account by carrying out molecular dynamics simulations of 10 ns in implicit water. The accuracy of the proposed method of calculation of pKa values is estimated from a test set of experimental pKa data for 297 ionizable residues from 34 proteins. The pKa-prediction test shows that, on average, 57, 86, and 95% of all predictions have an error lower than 0.5, 1.0, and 1.5 pKa units, respectively. This work contributes to our general understanding of the importance of protein flexibility for an accurate computation of pKa, providing critical insight about the significance of the multiple neutral states of acid and histidine residues for pKa-prediction, and may spur significant progress in our effort to develop a fast and accurate electrostatic-based method for pKa-predictions of proteins as a function of pH.
AB - A computational method, to predict the pKa values of the ionizable residues Asp, Glu, His, Tyr, and Lys of proteins, is presented here. Calculation of the electrostatic free-energy of the proteins is based on an efficient version of a continuum dielectric electrostatic model. The conformational flexibility of the protein is taken into account by carrying out molecular dynamics simulations of 10 ns in implicit water. The accuracy of the proposed method of calculation of pKa values is estimated from a test set of experimental pKa data for 297 ionizable residues from 34 proteins. The pKa-prediction test shows that, on average, 57, 86, and 95% of all predictions have an error lower than 0.5, 1.0, and 1.5 pKa units, respectively. This work contributes to our general understanding of the importance of protein flexibility for an accurate computation of pKa, providing critical insight about the significance of the multiple neutral states of acid and histidine residues for pKa-prediction, and may spur significant progress in our effort to develop a fast and accurate electrostatic-based method for pKa-predictions of proteins as a function of pH.
KW - continuum dielectric model
KW - molecular dynamics
KW - pKa-predictions
KW - protein ionization
UR - http://www.scopus.com/inward/record.url?scp=85013847820&partnerID=8YFLogxK
U2 - 10.1080/07391102.2017.1288169
DO - 10.1080/07391102.2017.1288169
M3 - Article
C2 - 28132613
AN - SCOPUS:85013847820
VL - 36
SP - 561
EP - 574
JO - Journal of Biomolecular Structure and Dynamics
JF - Journal of Biomolecular Structure and Dynamics
SN - 0739-1102
IS - 3
ER -
ID: 10351749