Department of Biophysics and Radiation Biology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
J Phys Chem B. 2011 Jun 2;115(21):6811-7. doi: 10.1021/jp108493g. Epub 2011 May 10.
Neutron scattering experiments have demonstrated that binding of the cancer drug methotrexate softens the low-frequency vibrations of its target protein, dihydrofolate reductase (DHFR). Here, this softening is fully reproduced using atomic detail normal-mode analysis. Decomposition of the vibrational density of states demonstrates that the largest contributions arise from structural elements of DHFR critical to stability and function. Mode-projection analysis reveals an increase of the breathing-like character of the affected vibrational modes consistent with the experimentally observed increased adiabatic compressibility of the protein on complexation.
中子散射实验表明，癌症药物甲氨蝶呤与二氢叶酸还原酶（DHFR）结合会使其低频振动变软。在这里，使用原子细节的正则模态分析完全再现了这种软化。振动态密度的分解表明，最大的贡献来自于 DHFR 的结构元素，这些元素对稳定性和功能至关重要。模式投影分析表明，受影响的振动模式的呼吸状特征增加，与复合物中蛋白质的绝热压缩性增加的实验观察结果一致。
