Hu Zhongqiao, Jiang Jianwen, Rajagopalan Raj
Department of Chemical and Biomolecular Engineering and The Singapore-MIT Alliance, National University of Singapore, Singapore.
Biophys J. 2007 Sep 1;93(5):1464-73. doi: 10.1529/biophysj.107.104646. Epub 2007 May 18.
A molecular thermodynamic model is developed to investigate the effects of macromolecular crowding on biochemical reactions. Three types of reactions, representing protein folding/conformational isomerization, coagulation/coalescence, and polymerization/association, are considered. The reactants, products, and crowders are modeled as coarse-grained spherical particles or as polymer chains, interacting through hard-sphere interactions with or without nonbonded square-well interactions, and the effects of crowder size and chain length as well as product size are examined. The results predicted by this model are consistent with experimentally observed crowding effects based on preferential binding or preferential exclusion of the crowders. Although simple hard-core excluded-volume arguments do in general predict the qualitative aspects of the crowding effects, the results show that other intermolecular interactions can substantially alter the extent of enhancement or reduction of the equilibrium and can even change the direction of the shift. An advantage of the approach presented here is that competing reactions can be incorporated within the model.
建立了一个分子热力学模型来研究大分子拥挤对生化反应的影响。考虑了三种类型的反应，分别代表蛋白质折叠/构象异构化、凝聚/聚结和聚合/缔合。反应物、产物和拥挤剂被建模为粗粒度的球形颗粒或聚合物链，通过硬球相互作用（有无非键方阱相互作用）进行相互作用，并研究了拥挤剂大小、链长以及产物大小的影响。该模型预测的结果与基于拥挤剂的优先结合或优先排斥的实验观察到的拥挤效应一致。虽然简单的硬核排除体积论点通常能预测拥挤效应的定性方面，但结果表明，其他分子间相互作用会显著改变平衡增强或降低的程度，甚至会改变转移方向。这里提出的方法的一个优点是，竞争反应可以纳入模型中。
