Yang Zhibo, Vorpagel Erich R, Laskin Julia
Chemical and Materials Sciences Division, Pacific Northwest National Laboratory, P.O. Box 999 (K8-88), Richland, WA 99352, USA.
Chemistry. 2009;15(9):2081-90. doi: 10.1002/chem.200802010.
Charge matters! The charge state significantly influences the conformation and the binding energy between vancomycin antibiotic and bacterial cell-wall analogue peptides (see figure). Surface-induced dissociation (SID) studies provide a quantitative comparison between the stabilities of different charge states of the complex.In this study we examined the effect of the charge state on the energetics and dynamics of dissociation of the noncovalent complex between the vancomycin and the cell-wall peptide analogue N(alpha),N(epsilon)-diacetyl-L-Lys-D-Ala-D-Ala (V-Ac(2)LKdAdA). The binding energies between the vancomycin and the peptide were obtained from the RRKM (Rice, Ramsperger, Kassel, Marcus) modeling of the time- and energy-resolved surface-induced dissociation (SID) experiments. Our results demonstrate that the stability of the complex towards fragmentation increases in the order: doubly protonated<singly protonated<deprotonated. Dissociation of the singly protonated and singly deprotonated complex is characterized by very large entropy effects, which indicate a substantial increase in the conformational flexibility of the resulting products. The experimental threshold energies of (1.75+/-0.08) eV ((40.3+/-1.8) kcal mol(-1)) and (1.34+/-0.08) eV ((30.9+/-1.8) kcal mol(-1)) obtained for the deprotonated and singly protonated complexes, respectively, are in excellent agreement with the results of density functional theory calculations. The increased stability of the deprotonated complex observed experimentally is attributed to the presence of three charged sites in the deprotonated complex, as compared with only one charged site in the singly protonated complex. The low binding energy of (0.93+/-0.04) eV ((21.4+/-0.9) kcal mol(-1)) obtained for the doubly protonated complex suggests that this ion is destabilized by Coulomb repulsion between the singly protonated vancomycin and the singly protonated peptide comprising the complex.
电荷至关重要！电荷状态显著影响万古霉素抗生素与细菌细胞壁类似物肽之间的构象和结合能（见图）。表面诱导解离（SID）研究对复合物不同电荷状态的稳定性进行了定量比较。在本研究中，我们考察了电荷状态对万古霉素与细胞壁肽类似物N（α），N（ε） - 二乙酰 - L - 赖氨酸 - D - 丙氨酸 - D - 丙氨酸（V - Ac₂LKdAdA）之间非共价复合物解离的能量学和动力学的影响。万古霉素与肽之间的结合能是通过对时间和能量分辨的表面诱导解离（SID）实验进行RRKM（赖斯、拉姆施佩格、卡塞尔、马库斯）建模得到的。我们的结果表明，复合物对碎片化的稳定性按以下顺序增加：双质子化＜单质子化＜去质子化。单质子化和单去质子化复合物的解离具有非常大的熵效应，这表明所得产物的构象灵活性大幅增加。去质子化和单质子化复合物分别获得的实验阈值能量（1.75±0.08）eV（（40.3±1.8）kcal mol⁻¹）和（1.34±0.08）eV（（30.9±1.8）kcal mol⁻¹）与密度泛函理论计算结果高度吻合。实验观察到的去质子化复合物稳定性增加归因于去质子化复合物中存在三个带电位点，而单质子化复合物中只有一个带电位点。双质子化复合物获得的低结合能（0.93±0.04）eV（（21.4±0.9）kcal mol⁻¹）表明，该离子因单质子化万古霉素与构成复合物的单质子化肽之间的库仑排斥而不稳定。
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