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

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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.

In: Journal of Biomolecular Structure and Dynamics, Vol. 36, No. 3, 17.02.2018, p. 561-574.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{798b688428554fbd83c396db09f20d0c,

title = "Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa{\textquoteright}s of proteins as a function of pH. Test on a large set of proteins",

abstract = "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.",

keywords = "continuum dielectric model, molecular dynamics, pKa-predictions, protein ionization",

author = "Vorobjev, {Yury N.} and Scheraga, {Harold A.} and Vila, {Jorge A.}",

note = "Publisher Copyright: {\textcopyright} 2017 Informa UK Limited, trading as Taylor & Francis Group.",

year = "2018",

month = feb,

day = "17",

doi = "10.1080/07391102.2017.1288169",

language = "English",

volume = "36",

pages = "561--574",

journal = "Journal of Biomolecular Structure and Dynamics",

issn = "0739-1102",

publisher = "Taylor and Francis Ltd.",

number = "3",

}

RIS

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.

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