Qin Sanbo, Mittal Jeetain, Zhou Huan-Xiang
Department of Physics and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.
Phys Biol. 2013 Aug;10(4):045001. doi: 10.1088/1478-3975/10/4/045001. Epub 2013 Aug 2.
We have developed a 'postprocessing' method for modeling biochemical processes such as protein folding under crowded conditions (Qin and Zhou 2009 Biophys. J. 97 12-19). In contrast to the direct simulation approach, in which the protein undergoing folding is simulated along with crowders, the postprocessing method requires only the folding simulation without crowders. The influence of the crowders is then obtained by taking conformations from the crowder-free simulation and calculating the free energies of transferring to the crowders. This postprocessing yields the folding free energy surface of the protein under crowding. Here the postprocessing results for the folding of three small proteins under 'repulsive' crowding are validated by those obtained previously by the direct simulation approach (Mittal and Best 2010 Biophys. J. 98 315-20). This validation confirms the accuracy of the postprocessing approach and highlights its distinct advantages in modeling biochemical processes under cell-like crowded conditions, such as enabling an atomistic representation of the test proteins.
我们已经开发出一种“后处理”方法，用于对诸如在拥挤条件下蛋白质折叠等生化过程进行建模（Qin和Zhou，2009年，《生物物理杂志》97卷，12 - 19页）。与直接模拟方法不同，在直接模拟方法中，正在折叠的蛋白质与拥挤剂一起被模拟，而后处理方法只需要进行无拥挤剂的折叠模拟。然后通过从无拥挤剂模拟中获取构象并计算转移到拥挤剂中的自由能，来得到拥挤剂的影响。这种后处理产生了蛋白质在拥挤条件下的折叠自由能表面。在此，三种小蛋白质在“排斥性”拥挤条件下折叠的后处理结果，通过之前直接模拟方法获得的结果得到了验证（Mittal和Best，2010年，《生物物理杂志》98卷，315 - 20页）。这种验证证实了后处理方法的准确性，并突出了其在模拟细胞样拥挤条件下生化过程中的独特优势，比如能够对测试蛋白质进行原子水平的表征。
