Predicting the Orientation of Adsorbed Proteins Steered with Electric Fields Using a Simple Electrostatic Model

Abstract

Under the most common experimental conditions, the adsorption of proteins to solid surfaces is a spontaneous process that leads to a rather compact layer of randomly oriented molecules. However, controlling such orientation is critically important for the development of catalytic surfaces. In this regard, the use of electric fields is one of the most promising alternatives. Our work is motivated by experimental observations that show important differences in catalytic activity of a trypsin-covered surface, which depended on the applied potential during the adsorption. Even though adsorption results from the combination of several processes, we were able to determine that (under the selected conditions) mean-field electrostatics play a dominant role, determining the orientation and yielding a difference in catalytic activity. We simulated the electrostatic potential numerically, using an implicit-solvent model based on the linearized Poisson–Boltzmann equation. This was implemented in an extension of the code PyGBe that included an external electric field, and rendered the electrostatic component of the solvation free energy. Our model (extensions available at the Github repository) allowed estimating the overall affinity of the protein with the surface, and their most likely orientation as a function of the potential applied. Our results show that the active sites of trypsin are, on average, more exposed when the electric field is negative, which agrees with the experimental results of catalytic activity, and confirm the premise that electrostatic interactions can be used to control the orientation of adsorbed proteins.

Arbitrary-Shape Dielectric Particles Interacting in the Linearized Poisson–Boltzmann Framework: An Analytical Treatment

“… 22 − 32 (See also the recent ref ( 33 ) for additional comments concerning the ranges of applicability of the DH theory.) This once again emphasizes the importance of a thorough study of the DH approximations, both theoretically and numerically, and justifies the constant stream of works related to the LPBE (see recent refs ( 2 , 5 , and 34 − 44 ), and references therein).…”

“…This, however, does not diminish the importance of studying the behavior of the LPBE also in the case of highly charged objects: their electrostatics may still be correctly described at sufficiently long distances (as compared to the Debye length) by the usual DH approximation provided that the sources of the electric field are properly renormalized. − (See also the recent ref for additional comments concerning the ranges of applicability of the DH theory.) This once again emphasizes the importance of a thorough study of the DH approximations, both theoretically and numerically, and justifies the constant stream of works related to the LPBE (see recent refs , , and − , and references therein).…”

Accurate Boundary Integral Formulations for the Calculation of Electrostatic Forces with an Implicit-Solvent Model

“…In the future, we plan to use this efficient approach in applications where high accuracy is required for reliable simulations. Some examples are the force induced on large structures, such as viruses and materials, and adsorption calculations, where we need to detect the influence of small changes in orientation ,, on the total force.…”

Accurate boundary-integral formulations for the calculation of electrostatic forces with an implicit-solvent model

“…Some examples are the force induced on large structures, such as viruses-materials, 15 and adsorption calculations, 50 where we need to detect the influence of small changes in orientation. 36,51,52 Graphical TOC Entry…”