Prediction of Protein Tertiary Structures by Monte Carlo Simulated Annealing and Multicanonical Algorithms

我们一直提倡在蛋白质折叠问题中使用蒙特卡罗模拟退火和多规范算法。虽然我们已经通过气相模拟测试了算法，但众所周知，溶剂的影响对蛋白质结构的形成和稳定性非常重要。因此，开发一种有效的模拟溶剂效应的方法是非常重要的。我们在三个不同的模型中测试了溶剂效应的包含。第一个是基于与溶剂可及表面积成正比的能量项。第二种是基于一个能量项，它代表了尺度粒子理论中的疏水效应。第三种是基于一个能量项，它代表了RISM理论中的所有溶剂效应。对于第一种可能性，我们比较了Met-enkephalin和Protein g的溶剂可及表面积的5种常用参数集的有效性。我们已经表明，5种参数集中有2种是不合适的。对于基于尺度粒子理论的第二种可能性，我们对Met-enkephalin进行了蒙特卡罗模拟退火模拟。我们发现所得到的最低能量构象比在气相模拟中得到的更广泛。这与核磁共振实验结果一致，表明Met-enkephalin在水溶液中被充分扩展。最后，在RISM理论的情况下，我们计算了我们准备的六种构象的溶剂化能进行比较。我们发现，在这六种结构中，完全伸展结构的总能量最低。我们现在准备开始用蒙特卡罗模拟退火和/或多规范算法进行严肃的模拟。

We have been advocating the use of Monte Carlo simulated annealing and multicanonical algorithms in the protein folding problem. Although we have been testing the algorithms by simulations in gas phase, it is well known that the effects of solvent are very important for the protein structure formation and stability. It is thus very important to develop an efficient method of inclusion of solvent effects in the simulations. We have tested the inclusion of solvent effects in three different models. First one is based on an energy term that is proportional to solvent accessible surface area. The second one is based on an energy term that represents hydrophobic effects by the scaled particle theory. The third one is based on an energy term that represents all the solvent effects by the RISM theory.For the first possiblity, we compared the validity of 5 commonly used parameter sets for the solvent accessible surface area for Met-enkephalin and Protein G.We have shown that two out of the five are inappropriate. For the second possibility that is based on the scaled particle theory, we performed Monte Carlo simulated annealing simulations for Met-enkephalin. We found that the lowest-energy conformation obtained is more extended than that obtained in gas-phase simulations. This is consistent with NMR experiments, Which indicates that Met-enkephalin is fully extended in aqueous solution. Finally, for the case of RISM theory, we calculated the solvation energies of six conformations that we prepared for comparison. We found that a fully extended structure has the lowest total energy among the six. We are now ready for starting serious simulations by Monte Carlo simulated annealing and/or multicanonical algorithms.