CXCR1, a member in G-protein coupled receptor (GPCR) family, binds to chemokine interleukin-8 (IL-8) specifically and transduces signals to mediate immune and inflammatory responses. Despite the importance of CXCR1, high-resolution structure determination is hindered by the challenges in crystallization. It has been shown that properly designed mutants with enhanced thermostability, together with fusion partner proteins, can be useful to form crystals for GPCR proteins. In this study, in silico protein design was carried out by using homology modeling and molecular dynamics simulations. To validate the computational modeling results, the thermostability of several mutants and the wild type were measured experimentally. Both computational results and experimental data suggest that the mutant L126W has a significant improvement in the thermostability. This study demonstrated that in silico design can guide protein engineering and potentially facilitate protein crystallography research.
Bibliographical noteFunding Information:
This project is supported by National Natural Science Foundation of China to Haiguang Liu (grant No. 11575021, U1530401, U1430237), NRF-2017R1A2B2008483 to Weontae Lee and NRF-2016R1A6A3A04010213 to Ji-Hye Yun through the National Research Foundation of Korea (NRF). This computational work is supported by the Tianhe-2JK computing time award at the Beijing Computational Research Center (CSRC) and Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund under Grant No. U1501501.
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