Department of Biotechnology and Life Sciences, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Koganei-shi, Nakamachi, Tokyo 184-8588, Japan.
Molecular Profiling Research Center for Drug Discovery (molprof), National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
Sci Rep. 2016 Jan 28;6:19479. doi: 10.1038/srep19479.
In order to investigate the contribution of individual amino acids to protein and peptide solubility, we carried out 100 ns molecular dynamics (MD) simulations of 10(6) Å(3) cubic boxes containing ~3 × 10(4) water molecules and 27 tetra-peptides regularly positioned at 23 Å from each other and composed of a single amino acid type for all natural amino acids but cysteine and glycine. The calculations were performed using Amber with a standard force field on a special purpose MDGRAPE-3 computer, without introducing any "artificial" hydrophobic interactions. Tetra-peptides composed of I, V, L, M, N, Q, F, W, Y, and H formed large amorphous clusters, and those containing A, P, S, and T formed smaller ones. Tetra-peptides made of D, E, K, and R did not cluster at all. These observations correlated well with experimental solubility tendencies as well as hydrophobicity scales with correlation coefficients of 0.5 to > 0.9. Repulsive Coulomb interactions were dominant in ensuring high solubility, whereas both Coulomb and van der Waals (vdW) energies contributed to the aggregations of low solubility amino acids. Overall, this very first all-atom molecular dynamics simulation of a multi-peptide system appears to reproduce the basic properties of peptide solubility, essentially in line with experimental observations.
为了研究氨基酸对蛋白质和肽溶解度的贡献，我们对包含约 3×10(4)个水分子和 27 个四肽的 10(6)Å(3)立方盒进行了 100ns 的分子动力学（MD）模拟，这些四肽彼此之间的距离为 23Å，且由除半胱氨酸和甘氨酸以外的所有天然氨基酸组成。使用 Amber 标准力场在专用 MDGRAPE-3 计算机上进行了计算，没有引入任何“人为”疏水性相互作用。由 I、V、L、M、N、Q、F、W、Y 和 H 组成的四肽形成了大的无定形簇，而由 A、P、S 和 T 组成的四肽形成了较小的簇。由 D、E、K 和 R 组成的四肽根本没有聚集。这些观察结果与实验溶解度趋势以及疏水性尺度很好地相关，相关系数为 0.5 到>0.9。排斥库仑相互作用是确保高溶解度的主要因素，而库仑和范德华（vdW）能量都有助于低溶解度氨基酸的聚集。总的来说，这是首次对多肽系统进行的全原子分子动力学模拟，似乎再现了肽溶解度的基本性质，与实验观察基本一致。
