Gromiha M Michael, Saraboji K, Ahmad Shandar, Ponnuswamy M N, Suwa Makiko
Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), Aomi Frontier Building 17F, 2-43 Aomi, Koto-ku, Tokyo 135-0064, Japan.
Biophys Chem. 2004 Feb 15;107(3):263-72. doi: 10.1016/j.bpc.2003.09.008.
Understanding the factors influencing the folding rate of proteins is a challenging problem. In this work, we have analyzed the role of non-covalent interactions for the folding rate of two-state proteins by free-energy approach. We have computed the free-energy terms, hydrophobic, electrostatic, hydrogen-bonding and van der Waals free energies. The hydrophobic free energy has been divided into the contributions from different atoms, carbon, neutral nitrogen and oxygen, charged nitrogen and oxygen, and sulfur. All the free-energy terms have been related with the folding rates of 28 two-state proteins with single and multiple correlation coefficients. We found that the hydrophobic free energy due to carbon atoms and hydrogen-bonding free energy play important roles to determine the folding rate in combination with other free energies. The normalized energies with total number of residues showed better results than the total energy of the protein. The comparison of amino acid properties with free-energy terms indicates that the energetic terms explain better the folding rate than amino acid properties. Further, the combination of free energies with topological parameters yielded the correlation of 0.91. The present study demonstrates the importance of topology for determining the folding rate of two-state proteins.
理解影响蛋白质折叠速率的因素是一个具有挑战性的问题。在这项工作中，我们通过自由能方法分析了非共价相互作用对两态蛋白质折叠速率的作用。我们计算了自由能项，包括疏水、静电、氢键和范德华自由能。疏水自由能被分为来自不同原子的贡献，如碳、中性氮和氧、带电氮和氧以及硫。所有自由能项都通过单相关系数和多相关系数与28种两态蛋白质的折叠速率相关联。我们发现，碳原子引起的疏水自由能和氢键自由能与其他自由能结合起来在决定折叠速率方面起着重要作用。用残基总数归一化的能量比蛋白质的总能量显示出更好的结果。氨基酸性质与自由能项的比较表明，能量项比氨基酸性质能更好地解释折叠速率。此外，自由能与拓扑参数的结合产生了0.91的相关性。本研究证明了拓扑结构在决定两态蛋白质折叠速率方面的重要性。
