Vibrational Softening of a Protein on Ligand Binding

被引：36

作者：

Balog, Erika ^{[2
]}

Perahia, David ^{[3
]}

Smith, Jeremy C. ^{[4
]}

Merzel, Franci ^{[1
]}

机构：

[1] Natl Inst Chem, Lab Mol Modeling, Ljubljana 1000, Slovenia

[2] Semmelweis Univ, Fac Med, Dept Biophys & Radiat Biol, H-1444 Budapest, Hungary

[3] Ecole Normale Super, F-94235 Cachan, France

[4] Univ Tennessee, Oak Ridge Natl Lab, Ctr Biophys Mol, Oak Ridge, TN 37831 USA

来源：

JOURNAL OF PHYSICAL CHEMISTRY B | 2011年 / 115卷 / 21期

基金：

美国国家科学基金会;

关键词：

COLI DIHYDROFOLATE-REDUCTASE; PANCREATIC TRYPSIN-INHIBITOR; NORMAL-MODE ANALYSIS; MOLECULAR-DYNAMICS; POINT MUTATIONS; FLEXIBLE LOOP; NMR RELAXATION; WATER; SIMULATIONS; STABILITY;

D O I：

10.1021/jp108493g

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

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.

引用

收藏

页码：6811 / 6817

页数：7

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