Effects of C-Terminal Lys-Arg Residue of AapA1 Protein on Toxicity and Structural Mechanism
Abstract
:1. Introduction
2. Results
2.1. Structural and Positional Changes of Tetrameric AapA1-28 Protein Elucidated through CMD_T1/2 Simulations
2.2. Two-Dimensional Free Energy Landscapes (FELs) from 2D-MetaD Simulations
2.3. Interactions between the AapA1-28 Protein and Membrane
Simulation Systems | Sampling Method | The Initial Conformation | Two Collective Variables (CVs) | Acronym | Simulation Length (ns) |
---|---|---|---|---|---|
Tetramer AapA1-28/POPE/POPG (3:1) | CMD simulation | Figure 1A | CMD_T1 | 5000 ns | |
Figure 1B | CMD_T2 | 5000 ns | |||
AapA1-28/POPE/POPG (3:1) | 2D-MetaD simulation | Figure 3C | CV1: Contact number between K-23 and the top phosphate group. CV2: Contact number between K-23 and the bottom phosphate group. | WT1 | 2 replica× 1000 ns |
AapA1-28/POPE/POPG (3:1) | 2D-MetaD simulation | Figure 3D | The same CVs | WT2 | 2 replica ×1000 ns |
AapA1-28/POPE/POPG (3:1) | CMD simulation | Figure 5A (representative conformation of region A in Figure 4) | CMD_M1 | 1000 ns | |
Figure 5B (representative conformation of region B in Figure 4) | CMD_M2 | 1000 ns | |||
Figure 5C (representative conformation of region A’ in Figure 4) | CMD_M3 | 1000 ns | |||
Figure 5D (representative conformation of region B’ in Figure 4) | CMD_M4 | 1000 ns | |||
Figure 5E (representative conformation of region C’ in Figure 4) | CMD_M5 | 1000 ns |
Contact Number | Protein Tilt Angle | ΔGbinding | ΔGelec | ΔGvdw | ΔGpols | ΔGnpols | |
---|---|---|---|---|---|---|---|
CMD_M1 | 10,965 ± 671 | 29.0 ± 6.7 | −1894 ± 130 | −2420 ± 164 | −619 ± 44 | 1224 ± 98 | −79 ± 3 |
CMD_M2 | 11,759 ± 658 | 16.7 ± 7.0 | −1933 ± 101 | −2506 ± 128 | −699 ± 38 | 1334 ± 158 | −61 ± 4 |
CMD_M3 | 10,931 ± 660 | 30.9 ± 6.1 | −1812 ± 143 | −2045 ± 263 | −664 ± 42 | 979 ± 212 | −82 ± 4 |
CMD_M4 | 11,547 ± 612 | 11.5 ± 4.5 | −1888 ± 115 | −2359 ± 134 | −661 ± 42 | 1193 ± 184 | −62 ± 6 |
CMD_M5 | 10,317 ± 640 | 23.7 ± 7.0 | −1741 ± 130 | −1970 ± 163 | −624 ± 39 | 930 ± 178 | −78 ± 4 |
2.4. Structural Characteristics of the AapA1-28 Protein Based on CMD_M Simulations
3. Discussion
4. Conclusions
5. Materials and Methods
5.1. MD Simulations for the AapA1-28 Tetramer-Containing Membrane Systems
5.2. D-MetaD Simulations for Single AapA1-28-Containing Membrane Systems
5.3. MD Simulations for Monomer AapA1-28-Containing Membrane Systems
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Prediction Methods | AapA1 (MATKHGKNSWKTLYLKISFLGCKVVVLLKR) | AapA1-28 (MATKHGKNSWKTLYLKISFLGCKVVVLL) |
---|---|---|
AMP_Scanner | AMP (0.98) | AMP (0.88) |
sAMPpred-GAT | AMP (0.70) | nonAMP (0.09) |
AI4AMP | AMP (0.60) | nonAMP (0.46) |
amPEPpy 1.0 | nonAMP (0.29) | nonAMP (0.37) |
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Cao, Z.; Zhao, L.; Yan, T.; Liu, L. Effects of C-Terminal Lys-Arg Residue of AapA1 Protein on Toxicity and Structural Mechanism. Toxins 2023, 15, 542. https://doi.org/10.3390/toxins15090542
Cao Z, Zhao L, Yan T, Liu L. Effects of C-Terminal Lys-Arg Residue of AapA1 Protein on Toxicity and Structural Mechanism. Toxins. 2023; 15(9):542. https://doi.org/10.3390/toxins15090542
Chicago/Turabian StyleCao, Zanxia, Liling Zhao, Tingting Yan, and Lei Liu. 2023. "Effects of C-Terminal Lys-Arg Residue of AapA1 Protein on Toxicity and Structural Mechanism" Toxins 15, no. 9: 542. https://doi.org/10.3390/toxins15090542