Probing Protein Structural Dynamics By Joint Analysis And Serial Crystallography

Direct visualization of functionally relevant protein dynamics is critical for the mechanistic understanding of many biochemical reactions and biological processes. However, it remains challenging to conduct dynamic crystallographic experiments at room temperature and to extract dynamic information from crystallography data. On the other hand, the crystal structures of the same protein family have been repeatedly determined and deposited to the Protein Data Bank (PDB). While each structure represents a snapshot of the protein structure, an ensemble of protein structures from the same system or family could convey dynamic information. In this dissertation, I will present three projects: (1) Uncovering the common characteristics of cholesterol binding sites in membrane proteins by examining the spatial distributions of cholesterol with respect to the protein framework in 57 PDB entries of the G-protein coupled receptor (GPCR) proteins. (2) Joint analysis of 527 GPCRs from Class A, B1, C and F using singular value decomposition (SVD) with a goal to identify the structural motions associated with GPCR activation. (3) The development of in situ serial crystallography platform to which I have made contributions as part of a larger effort to enable routine and robust dynamic crystallography experiments at room temperature

S1 Data -

(ZIP)</p

The forest plot results of DOR of S-Detect for diagnosis.

The forest plot results of DOR of S-Detect for diagnosis.</p

S1 Data -

(XLS)</p

Meta-regression analyses of potential source of heterogeneity.

(DOCX)</p

Heterogeneity analysis regression results.

Performance-based evaluation criteria (PBEC) are vital for selecting high-quality suppliers and achieving a PPP procurement performance. Through theoretical and institutional analysis, we found that the selection of PBEC centered on operations depends on the discretion of the purchaser. However, in an emerging and transforming PPP market, many factors have affected the scientific exercise of the purchaser’s discretion. This means that PPP projects must focus on construction and neglect operation in a certain period. Furthermore, to explore the influencing factors of the definition of PBEC, based on data of 9082 PPP projects between 2009 and 2021 in China, we adopted Ordinary Least Squares to empirically analyze two factors that influence the level of attention that is paid to the operation plan: corruption and accountability. The results indicate that the attention paid to the operation plan significantly increased with the reduction in corruption and the improvement in accountability. Robustness tests demonstrate the robustness of the results. A further heterogeneity analysis shows that the above factors have a more significant impact on non-state demonstration projects and projects with large investments. The contributions of this study are as follows: (1) Theoretically, this paper supplements the relevant research on evaluation criteria and provides new evidence on the impact of corruption and accountability on the defining PBEC. (2) Institutionally, it provides specific paths to limit the discretion of procurement officials when defining evaluation criteria. (3) In practice, it helps procurement officials to scientifically define PBEC and promote the realization of procurement performance.</div

Robustness tests−mediation model.

Robustness tests−mediation model.</p

The Forest map results of specificity and sensitivity of S-Detect for diagnosis.

The Forest map results of specificity and sensitivity of S-Detect for diagnosis.</p

S1 Dataset -

Performance-based evaluation criteria (PBEC) are vital for selecting high-quality suppliers and achieving a PPP procurement performance. Through theoretical and institutional analysis, we found that the selection of PBEC centered on operations depends on the discretion of the purchaser. However, in an emerging and transforming PPP market, many factors have affected the scientific exercise of the purchaser’s discretion. This means that PPP projects must focus on construction and neglect operation in a certain period. Furthermore, to explore the influencing factors of the definition of PBEC, based on data of 9082 PPP projects between 2009 and 2021 in China, we adopted Ordinary Least Squares to empirically analyze two factors that influence the level of attention that is paid to the operation plan: corruption and accountability. The results indicate that the attention paid to the operation plan significantly increased with the reduction in corruption and the improvement in accountability. Robustness tests demonstrate the robustness of the results. A further heterogeneity analysis shows that the above factors have a more significant impact on non-state demonstration projects and projects with large investments. The contributions of this study are as follows: (1) Theoretically, this paper supplements the relevant research on evaluation criteria and provides new evidence on the impact of corruption and accountability on the defining PBEC. (2) Institutionally, it provides specific paths to limit the discretion of procurement officials when defining evaluation criteria. (3) In practice, it helps procurement officials to scientifically define PBEC and promote the realization of procurement performance.</div

The liquidity risk-taking channel of monetary policy−mediation model.

The liquidity risk-taking channel of monetary policy−mediation model.</p