Conformation and dynamics of the three-helix bundle UBA domain of p62 from experiment and simulation

2008 ◽  
Vol 71 (1) ◽  
pp. 227-240 ◽  
Author(s):  
Clare-Louise Evans ◽  
Jed E. Long ◽  
Thomas R. A. Gallagher ◽  
Jonathan D. Hirst ◽  
Mark S. Searle
Keyword(s):  
Helix Bundle ◽  
Uba Domain ◽  
Experiment And Simulation

Experiment and Simulation of Erosion Behavior and Deformation Characteristics in Al6061-T6 Beam Due to Rhomboid Particle Impacts

2021 ◽  
Vol 69 (3) ◽  
Author(s):  
Mingchao Du ◽  
Zengliang Li ◽  
Xiangwei Dong ◽  
Chunyong Fan ◽  
Jiaqi Che ◽  
...  
Keyword(s):  
Deformation Characteristics ◽  
Erosion Behavior ◽  
Experiment And Simulation

scholarly journals Rational thermostabilisation of four-helix bundle dimeric de novo proteins

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shin Irumagawa ◽  
Kaito Kobayashi ◽  
Yutaka Saito ◽  
Takeshi Miyata ◽  
Mitsuo Umetsu ◽  
...  
Keyword(s):  
Protein Design ◽  
De Novo ◽  
Protein Complexes ◽  
Salt Bridge ◽  
Dynamics Simulation ◽  
Saturation Mutagenesis ◽  
Helix Bundle ◽  
Stable Mutant ◽  
Four Helix Bundle ◽  
The Stability

AbstractThe stability of proteins is an important factor for industrial and medical applications. Improving protein stability is one of the main subjects in protein engineering. In a previous study, we improved the stability of a four-helix bundle dimeric de novo protein (WA20) by five mutations. The stabilised mutant (H26L/G28S/N34L/V71L/E78L, SUWA) showed an extremely high denaturation midpoint temperature (Tm). Although SUWA is a remarkably hyperstable protein, in protein design and engineering, it is an attractive challenge to rationally explore more stable mutants. In this study, we predicted stabilising mutations of WA20 by in silico saturation mutagenesis and molecular dynamics simulation, and experimentally confirmed three stabilising mutations of WA20 (N22A, N22E, and H86K). The stability of a double mutant (N22A/H86K, rationally optimised WA20, ROWA) was greatly improved compared with WA20 (ΔTm = 10.6 °C). The model structures suggested that N22A enhances the stability of the α-helices and N22E and H86K contribute to salt-bridge formation for protein stabilisation. These mutations were also added to SUWA and improved its Tm. Remarkably, the most stable mutant of SUWA (N22E/H86K, rationally optimised SUWA, ROSA) showed the highest Tm (129.0 °C). These new thermostable mutants will be useful as a component of protein nanobuilding blocks to construct supramolecular protein complexes.

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