Volume 23, Issue 2
Accurate p$K_a$ Computation Using Matched Interface and Boundary (MIB) Method Based Poisson-Boltzmann Solver

Commun. Comput. Phys., 23 (2018), pp. 520-539.

Published online: 2018-02

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• Abstract

The p$K_a$ values are important quantities characterizing the ability of protein active sites to give up protons. p$K_a$ can be measured using NMR by tracing chemical-shifts of some special atoms, which is however expensive and time-consuming. Alternatively, p$K_a$ can be calculated numerically by electrostatic free energy changes subject to the protonation and deprotonation of titration sites. To this end, the Poisson-Boltzmann (PB) model is an effective approach for the electrostatics. However, numerically solving PB equation is challenging due to the jump conditions across the dielectric interfaces, irregular geometry of the molecular surface, and charge singularities. Our recently developed matched interface and boundary (MIB) method treats these challenges rigorously, resulting in a solid second order MIBPB solver. Since the MIBPB solver uses Green's function based regularization of charge singularities by decomposing the solution into a singular component and a regularized component, it is particularly efficient in treating the accuracy-sensitive, numerous, and complicated charge distributions from the p$K_a$ calculation. Our numerical results demonstrate that accurate free energies and p$K_a$ values are achieved at coarse grid rapidly. In addition, the resulting software, which pipelines the entire p$K_a$ calculation procedure, is available to all potential users from the greater bioscience community.

• Keywords

pKa, acid dissociation constant, Poisson-Boltzmann, finite difference, charge singularity.

92C40, 35J66

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@Article{CiCP-23-520, author = {}, title = {Accurate p$K_a$ Computation Using Matched Interface and Boundary (MIB) Method Based Poisson-Boltzmann Solver}, journal = {Communications in Computational Physics}, year = {2018}, volume = {23}, number = {2}, pages = {520--539}, abstract = {

The p$K_a$ values are important quantities characterizing the ability of protein active sites to give up protons. p$K_a$ can be measured using NMR by tracing chemical-shifts of some special atoms, which is however expensive and time-consuming. Alternatively, p$K_a$ can be calculated numerically by electrostatic free energy changes subject to the protonation and deprotonation of titration sites. To this end, the Poisson-Boltzmann (PB) model is an effective approach for the electrostatics. However, numerically solving PB equation is challenging due to the jump conditions across the dielectric interfaces, irregular geometry of the molecular surface, and charge singularities. Our recently developed matched interface and boundary (MIB) method treats these challenges rigorously, resulting in a solid second order MIBPB solver. Since the MIBPB solver uses Green's function based regularization of charge singularities by decomposing the solution into a singular component and a regularized component, it is particularly efficient in treating the accuracy-sensitive, numerous, and complicated charge distributions from the p$K_a$ calculation. Our numerical results demonstrate that accurate free energies and p$K_a$ values are achieved at coarse grid rapidly. In addition, the resulting software, which pipelines the entire p$K_a$ calculation procedure, is available to all potential users from the greater bioscience community.

}, issn = {1991-7120}, doi = {https://doi.org/10.4208/cicp.OA-2017-0078}, url = {http://global-sci.org/intro/article_detail/cicp/10536.html} }
TY - JOUR T1 - Accurate p$K_a$ Computation Using Matched Interface and Boundary (MIB) Method Based Poisson-Boltzmann Solver JO - Communications in Computational Physics VL - 2 SP - 520 EP - 539 PY - 2018 DA - 2018/02 SN - 23 DO - http://dor.org/10.4208/cicp.OA-2017-0078 UR - https://global-sci.org/intro/article_detail/cicp/10536.html KW - pKa, acid dissociation constant, Poisson-Boltzmann, finite difference, charge singularity. AB -

The p$K_a$ values are important quantities characterizing the ability of protein active sites to give up protons. p$K_a$ can be measured using NMR by tracing chemical-shifts of some special atoms, which is however expensive and time-consuming. Alternatively, p$K_a$ can be calculated numerically by electrostatic free energy changes subject to the protonation and deprotonation of titration sites. To this end, the Poisson-Boltzmann (PB) model is an effective approach for the electrostatics. However, numerically solving PB equation is challenging due to the jump conditions across the dielectric interfaces, irregular geometry of the molecular surface, and charge singularities. Our recently developed matched interface and boundary (MIB) method treats these challenges rigorously, resulting in a solid second order MIBPB solver. Since the MIBPB solver uses Green's function based regularization of charge singularities by decomposing the solution into a singular component and a regularized component, it is particularly efficient in treating the accuracy-sensitive, numerous, and complicated charge distributions from the p$K_a$ calculation. Our numerical results demonstrate that accurate free energies and p$K_a$ values are achieved at coarse grid rapidly. In addition, the resulting software, which pipelines the entire p$K_a$ calculation procedure, is available to all potential users from the greater bioscience community.

Jingzhen Hu, Shan Zhao & Weihua Geng. (2020). Accurate p$K_a$ Computation Using Matched Interface and Boundary (MIB) Method Based Poisson-Boltzmann Solver. Communications in Computational Physics. 23 (2). 520-539. doi:10.4208/cicp.OA-2017-0078
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