Macroscopic models for studies of electrostatic interactions in proteins: limitations and applicability.
Macroscopic models for studies of electrostatic interactions in proteins: limitations and applicability.
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DOI：
10.1073/pnas.81.15.4785
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发表时间：
1984-08
影响因子：
11.1
通讯作者：
A. Warshel;S. T. Russell;A. Churg
中科院分区：
文献类型：
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作者：
A. Warshel;S. T. Russell;A. Churg
检验了计算蛋白质静电能的宏观模型的有效性。将Tanford-Kirkwood （TK）模型扩展到包含电离基团的自能。证明了电离基团不可能存在于蛋白质的非极性区域，并认为蛋白质内部离子的实验发现证明了相应的局部环境是极性的。修正的TK模型（MTK模型）通过相应的溶剂可及性来调整电荷-电荷相互作用，但发现与它所基于的TK模型不一致。MTK模型对应于一个极性内部，而TK模型假设一个非极性内部。结果表明，假设蛋白质具有高介电常数的模型对平衡状态下带电基团之间的相互作用给出了合理的结果。然后解释了为什么蛋白质内部在带电基团周围是极性的，这与通常的看法相反。有人认为，在关注电荷-电荷相互作用时，人们忽视了蛋白质偶极子在决定蛋白质内部电荷的自能方面的关键贡献。
The validity of macroscopic models for calculations of electrostatic energies in proteins is examined. The Tanford-Kirkwood (TK) model is extended to include the self energy of the ionized groups. It is shown that ionized groups cannot exist inside nonpolar regions of proteins and argued that the experimental finding of ions inside proteins proves that the corresponding local environment is polar. The modified TK model (MTK model), which adjusts charge-charge interactions by the corresponding solvent accessibilities, is found to be inconsistent with the TK model, on which it is based. The MTK model corresponds to a polar interior whereas the TK model assumes a nonpolar interior. It is shown that models that assume a high dielectric constant for proteins give reasonable results for interactions between charged groups at equilibrium. It is then explained why, in contradiction to common belief, protein interiors are polar around charged groups. It is argued that in focusing on charge-charge interactions one overlooks the key contribution of the protein dipoles in determining the self energy of charges in the interior of proteins.