Structural Insights into Endostatin–Heparan Sulfate Interactions Using Modeling Approaches
Abstract
:1. Introduction
2. Results
2.1. Conventional Molecular Docking and MD Simulations
2.2. RS-REMD Analysis
2.3. Unbiased MD Simulation Analysis
2.4. Endostatin Mutations
3. Discussion
4. Materials and Methods
4.1. Endostatin’s Structure
4.2. Electrostatic Potential Calculations
4.3. Conventional Molecular Docking
4.4. Molecular Dynamics and MM-GBSA Calculations
4.5. Repulsive Scaling–Replica Exchange Molecular Dynamics (RS-REMD)
4.5.1. Molecular Dynamics Simulation
4.5.2. Binding Free Energy Calculations/Scoring
4.5.3. Refinement
4.5.4. MD Data Analysis
4.6. Unbiased MD Simulation
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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ΔG [kcal/mol] | GAG |
---|---|
−30.8 ± 8.5 | HP (GlcNS(6S)-IdoA(2S)) dp2, 1C4 |
−45.6 ± 7.7 | HP (GlcNS(6S)-IdoA(2S)) dp4, 1C4 |
−50.3 ± 11.0 | HP (GlcNS(6S)-IdoA(2S)) dp6, 1C4 |
−53.8 ± 17.9 | HP (GlcNS(6S)-IdoA(2S)) dp8, 1C4 |
−33.6 ± 7.2 | HP (GlcNS(6S)-IdoA(2S)) dp2, 2S0 |
−31.1 ± 5.7 | HP (GlcNS(6S)-IdoA(2S)) dp4, 2S0 |
−68.5 ± 14.4 | HP (GlcNS(6S)-IdoA(2S)) dp6, 2S0 |
−70.5 ± 14.9 | HP (GlcNS(6S)-IdoA(2S)) dp8, 2S0 |
−18.8 ± 4.2 | desulfated HS (GlcNAc-IdoA) dp2 |
−25.7 ± 4.2 | desulfated HS (GlcNAc-IdoA) dp4 |
−43.4 ± 1.8 | desulfated HS (GlcNAc-IdoA) dp6 |
−48 ± 13.6 | desulfated HS (GlcNAc-IdoA) dp8 |
−48.2 ± 8.8 | HS (GlcNS(6S)-GlcA) dp6 |
−47.7 ± 10.7 | HS (GlcNS-GlcA) dp6 |
−48.0 ± 12.1 | HS (GlcNS-IdoA(2S)) dp6, 1C4 |
−56.9 ± 11.1 | HS (GlcNS-IdoA(2S)) dp6, 2S0 |
ΔG (kcal/mol) | GAG |
---|---|
−62.5 ± 14.5 | HP (GlcNS(6S)-IdoA(2S))4 1C4 |
−51.8 ± 22.1 | (GlcNS(6S)-GlcA)4 |
−42.9 ± 13.3 | (GlcNS-GlcA)4 |
−49.2 ± 13.6 | (GlcNS-IdoA(2S))4 2S0 |
−51.9 ± 13.4 | (GlcNS-IdoA(2S))4 1C4 |
ΔG (kcal/mol) | Complex (n°) |
---|---|
−91.0 | 1 |
−106.7 | 2 |
−65.7 | 3 |
−71.4 | 4 |
−80.6 | 5 |
−87.3 | 6 |
−92.0 | 7 |
−88.9 | 8 |
−56.4 | 9 |
−79.3 | 10 |
−101.1 | 11 |
−94.1 | 12 |
−78.8 | 13 |
−67.4 | 14 |
−99.8 | 15 |
−52.9 | 16 |
−105.1 | 17 |
−84.0 | 18 |
−65.7 | 19 |
−79.5 | 20 |
ΔG [kcal/mol] | Amino Acid Residue |
---|---|
−3.9 | His1 |
−4.6 | Arg4 |
−8.0 | Arg24 |
−12.9 | Arg27 |
−5.9 | Arg38 |
−5.6 | Arg47 |
−10.8 | Arg53 |
−5.8 | Arg62 |
−7.8 | Arg63 |
−4.6 | Arg66 |
−2.8 | Lys75 |
−2.3 | Arg99 |
−2.9 | Lys106 |
−2.9 | Arg110 |
−2.4 | Lys117 |
−3.9 | Arg128 |
−4.5 | Arg129 |
−11.2 | Arg139 |
−2.4 | Arg156 |
ΔG [kcal/mol] | Mutant |
---|---|
−79.3 ± 14.5 | D30R |
−81.6 ± 15.5 | D56R |
−64.1 ± 10.3 | D65R |
−107.2 ± 12.7 | D30R, D56R |
−111.4 ± 19.8 | D30R, D56R, D65R |
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Uciechowska-Kaczmarzyk, U.; Frank, M.; Samsonov, S.A.; Maszota-Zieleniak, M. Structural Insights into Endostatin–Heparan Sulfate Interactions Using Modeling Approaches. Molecules 2024, 29, 4040. https://doi.org/10.3390/molecules29174040
Uciechowska-Kaczmarzyk U, Frank M, Samsonov SA, Maszota-Zieleniak M. Structural Insights into Endostatin–Heparan Sulfate Interactions Using Modeling Approaches. Molecules. 2024; 29(17):4040. https://doi.org/10.3390/molecules29174040
Chicago/Turabian StyleUciechowska-Kaczmarzyk, Urszula, Martin Frank, Sergey A. Samsonov, and Martyna Maszota-Zieleniak. 2024. "Structural Insights into Endostatin–Heparan Sulfate Interactions Using Modeling Approaches" Molecules 29, no. 17: 4040. https://doi.org/10.3390/molecules29174040