Molecular dynamics characterisations of the Trp-cage folding mechanisms: in the absence and presence of water solvents

Abstract

2012) Molecular dynamics characterisations of the Trp-cage folding mechanisms: in the absence and presence of water solvents, Molecular Simulation, 38:2, 161-171, Protein folding is an important and yet challenging topic in current molecular biology. In this work, the folding dynamics and mechanisms of the Trp-cage mini-protein were studied with molecular dynamics simulations, in the absence and presence of water solvents. The important intermediates during the Trp-cage folding were determined by gradually decreasing the simulation temperature. The folding transition temperature was identified to be approximately 400 K, and the folding pathway was decomposed into six steps: U $ I 1 $ I 2 $ I 3 $ I 4 $ F 1 $ F 2 , where U, I and F represent the unfolded, intermediate and folded states, respectively. The finding that the two helical subunits are successively formed is consistent with the experimental observations, and the Asp9/Arg16 salt bridge forms at the final stage and does not play a significant role during folding kinetics. The presence of water solvents induces hydrophobic collapse as the whole cage comparatively closes. Within aqueous solutions, the Trp-cage folding begins to contract into the meta-stable state, and by traversing the transition state it arrives at the native-like structure, which resembles the experimental structure closely.

Folding of a Zinc-Finger ββα-Motif Investigated Using Two-Dimensional and Time-Resolved Vibrational Spectroscopy

“…At high temperature, this α-helix cross-peak signature decreases in intensity, but does not disappear, indicating that a considerable amount of α-helical structure remains present in the thermally denatured state at 333 K, when only 28% of the peptide is in the native conformation (determined from the UV-CD amplitude, Figure a). This indicates that the α-helix is thermally more stable than the other structural elements of FSD-1, in agreement with previous studies. ,− ,, At 333 K, the fraction of the natively folded population has decreased to 28% of its value at 275 K (Figure a), while the α-helix cross-peak intensity at 333 K has only decreased to 60% of its value at 275 K (as determined from the α helix cross peak intensity, Figure d and h). The FTIR intensity at the α-helix cross-peak frequency (1638 cm –1 ) decreases by 31%, a value similar to the 40% decrease in the α helix cross-peak intensity.…”

“…This indicates that the α-helix is thermally more stable than the other structural elements of FSD-1, in agreement with previous studies. 19,[21][22][23]25,42 At 333 K, the fraction of the natively folded population has decreased to 28% of its value at 275 K (Figure 3a), while the α-helix crosspeak intensity at 333 K has only decreased to 60% of its value at 275 K (as determined from the α helix cross peak intensity, Figure 4d and h). The FTIR intensity at the α-helix cross-peak frequency (1638 cm −1 ) decreases by 31%, 43 a value similar to the 40% decrease in the α helix cross-peak intensity.…”

An interoperable implementation of collective‐variable based enhanced sampling methods in extended phase space within the OpenMM package

“…Based on earlier reports, 92,[115][116][117] we chose eight CVs for the that will be explained in Section 3.1, we found that scaling up the values of CVs is important in certain cases to facilitate CV oscillation about the corresponding auxiliary variables. The parameters μ and κ chosen for the (scaled) CVs are listed in Table 1.…”

Computational and experimental studies on the influence of theTrp-cage inter-residue interactions and other external factors on its structural and folding stability

“…研究还发现, 目前还存在一些力场对Trp-cage折叠 热力学行为的描述不够准确. 例如, Zhou [56] 和Paschek 等人 [89] 分别发现, OPLSAA/L和AMBER ff94力场计算 得到的折叠熔融温度为400 K和450 K, 显著高于实验 观察值315 K [15,17,18] ; 尽管Garcia课题组 [15,17,87] . Kim等 人 [64] 通过对模拟轨迹分析发现, 尽管盐桥的早期形成 图 4 模型蛋白Trp-cage在285 K, 300 K, 315 K和325 K温度下的折叠动力学网络 [75~77] .…”