Temperature-induced unfolding of epidermal growth factor (EGF): insight from molecular dynamics simulation.
Temperature-induced unfolding of epidermal growth factor (EGF): insight from molecular dynamics simulation.
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DOI：
10.1016/j.jmgm.2010.03.011
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发表时间：
2010-08-24
影响因子：
2.9
通讯作者：
Ren, Pengyu
中科院分区：
文献类型：
--
作者：
Yan, Chunli;Pattani, Varun;Tunnell, James W.;Ren, Pengyu
关键词：
蛋白质结构和功能的热破坏是一种潜在的强大的治疗工具。随着新兴的纳米粒子靶向和飞秒激光技术，有可能将局部加热传递到特定分子。因此，重要的是要了解蛋白质在高温下（如接近水沸点）展开或失去功能的速度。在这项研究中，表皮生长因子的热损伤进行了研究，结合复制品交换（136副本）和传统的分子动力学模拟。采用REMD模拟来严格探索EGF展开的自由能景观。有趣的是，除了原生和未折叠状态，我们还观察到一个独特的熔融球（MG）状态，保留了大量的原生接触。基于EGF去折叠是一个三态过程的认识，我们研究了EGF去折叠的动力学（N→ MG→h）多个20-ns的常规MD模拟。从模拟中确定的Arabius前因子和活化能势垒在以前研究的蛋白质的范围内。与在相对低的温度下以秒至小时的时间尺度发生的细胞和组织的热损伤相反，当热浴的温度接近沸点时，蛋白质的变性发生在纳秒内。
Thermal disruption of protein structure and function is a potentially powerful therapeutic vehicle. With the emerging nanoparticle-targeting and femtosecond laser technology, it is possible to deliver heating locally to specific molecules. It is therefore important to understand how fast a protein can unfold or lose its function at high temperatures, such as near the water boiling point. In this study, the thermal damage of EGF was investigated by combining the replica exchange (136 replicas) and conventional molecular dynamics simulations. The REMD simulation was employed to rigorously explore the free energy landscape of EGF unfolding. Interestingly, besides the native and unfolded states, we also observed a distinct molten globule (MG) state that retained substantial amount of native contacts. Based on the understanding that which the unfolding of EGF is a three-state process, we have examined the unfolding kinetics of EGF (N→ MG→h multiple 20-ns conventional MD simulations. The Arrhenius prefactors and activation energy barriers determined from the simulation are within the range of previously studied proteins. In contrast to the thermal damage of cells and tissues which take place on the time scale of seconds to hours at relatively low temperatures, the denaturation of proteins occur in nanoseconds when the temperature of heat bath approaches the boiling point.
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DOI：
10.1073/pnas.2232479100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Hirsch, LR;Stafford, RJ;West, JL
通讯作者：
West, JL
DOI：
10.1073/pnas.2335541100
发表时间：
2003-11-25
影响因子：
11.1
作者：
García, AE;Onuchic, JN
通讯作者：
Onuchic, JN
影响因子：
5.5
作者：
Hess, Berk
通讯作者：
Hess, Berk
影响因子：
4.4
作者：
ESSMANN, U;PERERA, L;PEDERSEN, LG
通讯作者：
PEDERSEN, LG
影响因子：
6.3
作者：
BERENDSEN, HJC;VANDERSPOEL, D;VANDRUNEN, R
通讯作者：
VANDRUNEN, R