A New DelPhi Feature for Modeling Electrostatic Potential around Proteins: Role of Bound Ions and Implications for Zeta-Potential

Abstract

A new feature of the popular software DelPhi is developed and reported, allowing for computing the surface averaged electrostatic potential (SAEP) of macromolecules. The user is given the option to specify the distance from the van der Waals surface where the electrostatic potential will be outputted. In conjunction with DelPhiPKa and the BION server, the user can adjust the charges of titratable groups according to specific pH values, and add explicit ions bound to the macromolecular surface. This approach is applied to a set of four proteins with "experimentally" delivered zeta (ζ)-potentials at different pH values and salt concentrations. It has been demonstrated that the protocol is capable of predicting ζ-potentials in the case of proteins with relatively large net charges. This protocol has been less successful for proteins with low net charges. The work demonstrates that in the case of proteins with large net charges, the electrostatic potential should be collected at distances about 4 Å away from the vdW surface and explicit ions should be added at a binding energy cutoff larger than 1-2kT, in order to accurately predict ζ-potentials. The low salt conditions substantiate this effect of ions on SAEP.

Protein surface functionalisation as a general strategy for facilitating biomimetic mineralisation of ZIF-8

“…Both the surface electrostatic potential (zeta potential) and pI of a protein, both of which we have shown to be good discriminators of a protein's ability to seed ZIF-8 formation, can be determined from theory. 37 – 39 Therefore, whether a protein is likely to undergo biomimetic mineralisation can be predicted prior to experimental study.…”

“…S11–S13 † ). 37 , 41 The calculated surface potential also provides comprehensive 3D information about the electrostatic interactions of the protein with the surrounding electrolyte solution. Fig.…”

“…Using the SURFPOT module 37 within the DELPHI software 41 the linearised Poisson–Boltzmann equation, 56 ∇ · [ ε ( r )∇ ψ ( r )] – ε 0 ε r κ ( r ) 2 ψ ( r ) = – ρ ( r ), was solved to calculate the electrostatic potential, ψ ( r ), at position r . In the expression, ρ ( r ) is the (fixed) charge density of the solute (protein), ε ( r ) is the spatially varying dielectric permittivity, which is different in the protein and in the solution, and κ ( r ) is the Debye screening parameter given by outside of the protein and is zero inside of the protein.…”

DelPhi Suite: New Developments and Review of Functionalities

“…Details are described in the corresponding paper. [46] Surface-free approach of computing pKa's of proteins, RNAs, and DNAs. Computing proton equilibria or predicting pKa's of ionizable group has been explored by many researchers.…”

BION-2: Predicting Positions of Non-Specifically Bound ions on Protein Surface by a Gaussian-based Treatment of Electrostatic Environment

“…Surface-bound ions are essential for reducing the effective net charge of macromolecules and their effect is manifested via Zeta potential [18,19]. It was demonstrated that accounting for surface-bound ions is crucial for modeling experimentally measured Zeta potential for various proteins [20]. The list of examples can be extended; however, it is evident non-specifically surface-bound ions are essential for many biological processes.…”