Folding Simulations of an α‑Helical Hairpin Motif αtα with Residue-Specific Force Fields

α-Helical hairpin (two-helix bundle) is a structure motif composed of two interacting helices connected by a turn or a short loop. It is an important model for protein folding studies, filling the gap between isolated α-helix and larger all-α domains. Here, we present, for the first time, successful folding simulations of an α-helical hairpin. Our RSFF1 and RSFF2 force fields give very similar predicted structures of this αtα peptide, which is in good agreement with its NMR structure. Our simulations also give site-specific stability of α-helix formation in good agreement with amide hydrogen exchange experiments. Combining the folding free energy landscapes and analyses of structures sampled in five different ranges of the fraction of native contacts (<i>Q</i>), a folding mechanism of αtα is proposed. The most stable sites of Q9-E15 in helix-1 and E24-A30 in helix-2 close to the loop region act as the folding initiation sites. The formation of interhelix side-chain contacts also initiates near the loop region, but some residues in the central parts of the two helices also form contacts quite early. The two termini fold at a final stage, and the loop region remains flexible during the whole folding process. This mechanism is similar to the “zipping out” pathway of β-hairpin folding

Mechanism of Phosphorylation-Induced Folding of 4E-BP2 Revealed by Molecular Dynamics Simulations

Site-specific phosphorylation of an intrinsically disordered protein, eIF4E-binding protein isoform 2 (4E-BP2), can suppress its native function by folding it into a four-stranded β-sheet, but the mechanism of this phosphorylation-induced folding is unclear. In this work, we use all-atom molecular dynamics simulations to investigate both the folded and unfolded states of 4E-BP2 under different phosphorylation states of T37 and T46. The results show that the phosphorylated forms of both T37 and T46 play important roles in stabilizing the folded structure, especially for the β-turns and the sequestered binding motif. The phosphorylated residues not only guide the folding of the protein through several intermediate states but also affect the conformational distribution of the unfolded ensemble. Significantly, the phosphorylated residues can function as nucleation sites for the folding of the protein by forming certain local structures that are stabilized by hydrogen bonding involving the phosphate group. The region around phosphorylated T46 appears to fold before that around phosphorylated T37. These findings provide new insight into the intricate effects of protein phosphorylation

Impact of two types of El Niño events and La Niña event on <i>Nilaparvata lugens</i> (Stål) in South China

这些数据包括厄尔尼诺和拉尼娜事件的指标，以及华南地区褐飞虱侵染和发生水平的数据。</p

Unveiling the State Transition Mechanisms of Ras Proteins through Enhanced Sampling and QM/MM Simulations

In cells, wild-type RasGTP complexes exist in two distinct states: active State 2 and inactive State 1. These complexes regulate their functions by transitioning between the two states. However, the mechanisms underlying this state transition have not been clearly elucidated. To address this, we conducted a detailed simulation study to characterize the energetics of the stable states involved in the state transitions of the HRasGTP complex, specifically from State 2 to State 1. This was achieved by employing multiscale quantum mechanics/molecular mechanics and enhanced sampling molecular dynamics methods. Based on the simulation results, we constructed the two-dimensional free energy landscapes that provide crucial information about the conformational changes of the HRasGTP complex from State 2 to State 1. Furthermore, we also explored the conformational changes from the intermediate state to the product state during guanosine triphosphate hydrolysis. This study on the conformational changes involved in the HRas state transitions serves as a valuable reference for understanding the corresponding events of both KRas and NRas as well

Additional file 1: of Aggregation of lipid rafts activates c-met and c-Src in non-small cell lung cancer cells

Table S1. Colony-plating efficiency (PE) of A549 cells treated with either control or MβCD followed by irradiation. (DOC 28 kb

Additional file 5: of Aggregation of lipid rafts activates c-met and c-Src in non-small cell lung cancer cells

Table S5. The percentage of protein expressed in lipid rafts out of the whole-cell samples in A549 cells. (DOC 28 kb

Additional file 2: of Aggregation of lipid rafts activates c-met and c-Src in non-small cell lung cancer cells

Table S2. Colony-plating efficiency (PE) of H1993 cells treated with either control or MβCD followed by irradiation. (DOC 29 kb

Additional file 4: of Aggregation of lipid rafts activates c-met and c-Src in non-small cell lung cancer cells

Table S4. Expression of proteins in lipid rafts under different conditions in A549 cells. (DOC 28 kb

1N3R-tau induces S phase arrest in HEK293 cells.

<p><b>(A)</b> The distribution of HEK293 with six tau isoforms in sub G1 phase. <b>(B)</b> The distribution of HEK293 with six tau isoforms in G1 phase. *<i>P</i> < 0.05, compared with vector. <b>(C)</b> The distribution of HEK293 with six tau isoforms in S phase. **<i>P</i> < 0.01, compared with vector. <b>(D)</b> The distribution of HEK293 with six tau isoforms in G2/M phase. *<i>P</i> < 0.05, compared with vector.</p

1N3R-tau inhibits cell proliferation measured by BrdU incorporation.

<p>Fluorescent micrographs of eGFP and BrdU expression with six tau isoforms in N2a cells after 48 h transfection. GFP (Green), BrdU (Red). Quantification of BrdU-positive cells in eGFP expressing N2a cells with six tau isoforms after 48 h transfection. Scale bar = 50 μm. All values are standardized with vector. *<i>P</i> < 0.05, compared with vector.</p