TY - JOUR
T1 - Over-Destabilization of Protein-Protein Interaction in Generalized Born Model and Utility of Energy Density Integration Cutoff
AU - Mizuhara, Yukinobu
AU - Parkin, Dan
AU - Umezawa, Koji
AU - Ohnuki, Jun
AU - Takano, Mitsunori
N1 - Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/5/11
Y1 - 2017/5/11
N2 - The generalize Born (GB) model is frequently used in MD simulations of biomolecular systems in aqueous solution. The GB model is usually based on the so-called Coulomb field approximation (CFA) for the energy density integration. In this study, we report that the GB model with CFA overdestabilizes the long-range electrostatic attraction between oppositely charged molecules (ionic bond forming two-helix system and kinesin-tubulin system) when the energy density integration cutoff, rmax, which is used to calculate the Born energy, is set to a large value. We show that employing large rmax, which is usually expected to make simulation results more accurate, worsens the accuracy so that the attraction is changed into repulsion. It is demonstrated that the overdestabilization is caused by the overestimation of the desolvation penalty upon binding that originates from CFA. We point out that the overdestabilization can be corrected by employing a relatively small cutoff (rmax = 10-15 Å), affirming that the GB models, even with CFA, can be used as a powerful tool to theoretically study the protein-protein interaction, particularly on its dynamical aspect, such as binding and unbinding.
AB - The generalize Born (GB) model is frequently used in MD simulations of biomolecular systems in aqueous solution. The GB model is usually based on the so-called Coulomb field approximation (CFA) for the energy density integration. In this study, we report that the GB model with CFA overdestabilizes the long-range electrostatic attraction between oppositely charged molecules (ionic bond forming two-helix system and kinesin-tubulin system) when the energy density integration cutoff, rmax, which is used to calculate the Born energy, is set to a large value. We show that employing large rmax, which is usually expected to make simulation results more accurate, worsens the accuracy so that the attraction is changed into repulsion. It is demonstrated that the overdestabilization is caused by the overestimation of the desolvation penalty upon binding that originates from CFA. We point out that the overdestabilization can be corrected by employing a relatively small cutoff (rmax = 10-15 Å), affirming that the GB models, even with CFA, can be used as a powerful tool to theoretically study the protein-protein interaction, particularly on its dynamical aspect, such as binding and unbinding.
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U2 - 10.1021/acs.jpcb.7b01438
DO - 10.1021/acs.jpcb.7b01438
M3 - Article
C2 - 28426223
AN - SCOPUS:85020169628
VL - 121
SP - 4669
EP - 4677
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
SN - 1089-5647
IS - 18
ER -