Dissecting the Structural Dynamics of Authentic Cholesteryl Ester Transfer Protein for the Discovery of Potential Lead Compounds: A Theoretical Study
Abstract
:1. Introduction
2. Results and Discussion
2.1. Contrast in Structural Stability and Flexibility
2.2. Contrast in the N-Terminal End, C-Terminal End, and “Neck” of the Hydrophobic Tunnel
2.3. Virtual Screening for CETP
2.4. Structural Dynamics Analysis upon Ligand Binding
3. Materials and Methods
3.1. System Preparation
3.2. MD Simulations
3.3. Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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CETPMutant | CETPAuthentic | |||||
---|---|---|---|---|---|---|
Region | Hydrophobic | Hydrophilic | Total | Hydrophobic | Hydrophilic | Total |
N-end 2 | −0.05 | 0.02 | −0.04 | −0.05 | 0.00 | −0.02 |
C-end 3 | −0.02 | 0.08 | 0.05 | 0.07 | 0.08 | 0.08 |
Ω1 | −0.13 | 0.09 | −0.05 | 0.04 | 0.04 | 0.04 |
Ω2 | 0.15 | 0.03 | 0.18 | 0.19 | 0.18 | 0.19 |
Ω3 | 0.05 | 0.08 | 0.12 | 0.05 | 0.10 | 0.09 |
Ω4 | 0.08 | 0.05 | 0.13 | 0.04 | 0.01 | 0.02 |
Ω5 | −0.08 | −0.07 | −0.15 | −0.08 | −0.06 | −0.07 |
Ω6 | −0.15 | 0.07 | −0.08 | −0.10 | 0.05 | 0.00 |
Helix X | 0.02 | 0.03 | 0.06 | 0.10 | 0.01 | 0.03 |
ZINC ID | ΔEele 2 | ΔEvdw 3 | ΔGsur 4 | ΔGGB 5 | ΔGbind |
---|---|---|---|---|---|
ZINC000002010603 | −2.2 ± 1.5 | −14.2 ± 0.9 | −8.9 ± 0.5 | 1.7 ± 0.1 | −23.6 ± 0.2 |
ZINC000006248133 | −5.5 ± 2.0 | −12.6 ± 1.0 | −8.4 ± 0.7 | 1.1 ± 1.5 | −25.4 ± 2.1 |
ZINC000005871812 | −5.6 ± 1.8 | −13.1 ± 1.1 | −8.7 ± 0.7 | 2.0 ± 1.3 | −25.4 ± 2.1 |
ZINC000002261174 | −5.8 ± 1.4 | −19.5 ± 0.9 | −12.3 ± 0.6 | 2.5 ± 1.0 | −35.0 ± 1.7 |
ZINC000003526223 | 0.0 ± 0.5 | −0.1 ± 0.9 | −0.1 ± 0.7 | −0.1 ± 0.4 | −0.2 ± 0.2 |
ZINC000005871644 | −2.6 ± 1.4 | −14.9 ± 1.2 | −9.7 ± 0.8 | 0.9 ± 1.1 | −26.3 ± 2.3 |
ZINC000007067674 | −2.2 ± 1.4 | −11.3 ± 1.5 | −7.0 ± 0.1 | 0.7 ± 1.1 | −19.7 ± 2.8 |
ZINC000006242926 | −2.5 ± 1.1 | −19.5 ± 0.8 | −11.2 ± 0.5 | 0.6 ± 0.9 | −32.6 ± 1.5 |
ZINC ID | ΔEele 2 | ΔEvdw 3 | ΔGsur 4 | ΔGGB 5 | ΔGbind |
---|---|---|---|---|---|
ZINC000002010603 | −5.8 ± 3.1 | −17.5 ± 1.1 | −10.1 ± 0.7 | 0.4 ± 2.7 | −32.9 ± 2.3 |
ZINC000006248133 | −9.1 ± 2.3 | −19.6 ± 0.8 | −13.0 ± 0.6 | 3.2 ± 2.0 | −38.8 ± 1.6 |
ZINC000005871812 | −2.8 ± 1.6 | −26.6 ± 0.8 | −15.5 ± 0.4 | −0.4 ± 1.3 | −45.3 ± 1.3 |
ZINC000002261174 | −2.7 ± 1.3 | −19.0 ± 0.9 | −11.5 ± 0.6 | −0.3 ± 1.1 | −33.5 ± 1.8 |
ZINC000003526223 | −7.0 ± 1.7 | −28.5 ± 0.8 | −16.5 ± 0.5 | 5.5 ± 1.6 | −46.5 ± 1.3 |
ZINC000005871644 | −5.1 ± 1.6 | −23.1 ± 0.8 | −14.3 ± 0.5 | 3.1 ± 1.4 | −39.4 ± 1.4 |
ZINC000007067674 | −2.3 ± 1.2 | −26.1 ± 0.6 | −15.6 ± 0.3 | 0.6 ± 1.1 | −43.4 ± 1.0 |
ZINC000006242926 | −1.4 ± 1.2 | −25.9 ± 0.9 | −15.0 ± 0.5 | 0.1 ± 1.1 | −42.2 ± 1.4 |
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Zhao, Y.; Hao, D.; Zhao, Y.; Zhang, S.; Zhang, L.; Yang, Z. Dissecting the Structural Dynamics of Authentic Cholesteryl Ester Transfer Protein for the Discovery of Potential Lead Compounds: A Theoretical Study. Int. J. Mol. Sci. 2023, 24, 12252. https://doi.org/10.3390/ijms241512252
Zhao Y, Hao D, Zhao Y, Zhang S, Zhang L, Yang Z. Dissecting the Structural Dynamics of Authentic Cholesteryl Ester Transfer Protein for the Discovery of Potential Lead Compounds: A Theoretical Study. International Journal of Molecular Sciences. 2023; 24(15):12252. https://doi.org/10.3390/ijms241512252
Chicago/Turabian StyleZhao, Yizhen, Dongxiao Hao, Yifan Zhao, Shengli Zhang, Lei Zhang, and Zhiwei Yang. 2023. "Dissecting the Structural Dynamics of Authentic Cholesteryl Ester Transfer Protein for the Discovery of Potential Lead Compounds: A Theoretical Study" International Journal of Molecular Sciences 24, no. 15: 12252. https://doi.org/10.3390/ijms241512252
APA StyleZhao, Y., Hao, D., Zhao, Y., Zhang, S., Zhang, L., & Yang, Z. (2023). Dissecting the Structural Dynamics of Authentic Cholesteryl Ester Transfer Protein for the Discovery of Potential Lead Compounds: A Theoretical Study. International Journal of Molecular Sciences, 24(15), 12252. https://doi.org/10.3390/ijms241512252