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Electrostatic component of binding energy: Interpreting predictions from poisson–boltzmann equation and modeling protocols
Author(s) -
Chakavorty Arghya,
Li Lin,
Alexov Emil
Publication year - 2016
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.24475
Subject(s) - force field (fiction) , electrostatics , poisson–boltzmann equation , statistical physics , molecular dynamics , robustness (evolution) , sensitivity (control systems) , component (thermodynamics) , boltzmann constant , field (mathematics) , electric potential energy , chemistry , computational chemistry , energy (signal processing) , biological system , physics , thermodynamics , mathematics , quantum mechanics , engineering , ion , biochemistry , organic chemistry , electronic engineering , biology , pure mathematics , gene
Macromolecular interactions are essential for understanding numerous biological processes and are typically characterized by the binding free energy. Important component of the binding free energy is the electrostatics, which is frequently modeled via the solutions of the Poisson–Boltzmann Equations (PBE). However, numerous works have shown that the electrostatic component (ΔΔ G elec ) of binding free energy is very sensitive to the parameters used and modeling protocol. This prompted some researchers to question the robustness of PBE in predicting ΔΔ G elec . We argue that the sensitivity of the absolute ΔΔ G elec calculated with PBE using different input parameters and definitions does not indicate PBE deficiency, rather this is what should be expected. We show how the apparent sensitivity should be interpreted in terms of the underlying changes in several numerous and physical parameters. We demonstrate that PBE approach is robust within each considered force field (CHARMM‐27, AMBER‐94, and OPLS‐AA) once the corresponding structures are energy minimized. This observation holds despite of using two different molecular surface definitions, pointing again that PBE delivers consistent results within particular force field. The fact that PBE delivered ΔΔ G elec values may differ if calculated with different modeling protocols is not a deficiency of PBE, but natural results of the differences of the force field parameters and potential functions for energy minimization. In addition, while the absolute ΔΔ G elec values calculated with different force field differ, their ordering remains practically the same allowing for consistent ranking despite of the force field used. © 2016 Wiley Periodicals, Inc.