A Molecular Docking Study Reveals That Short Peptides Induce Conformational Changes in the Structure of Human Tubulin Isotypes αβI, αβII, αβIII and αβIV
Abstract
:1. Introduction
2. Material and Methods
2.1. Peptide Screening and Preparation
2.2. Homology Modeling and Protein Preparation
2.3. Molecular Docking
2.4. Molecular Dynamics
2.5. Post Molecular Dynamics MM-GBSA
2.6. Physicochemical, Allergenicity, and Toxicity Prediction
3. Results and Discussion
3.1. Peptide-αβI-Tubulin Complex
3.2. Peptide-αβII-Tubulin Receptor Complex
3.3. Peptides-αβIII-Tubulin Dimer Complex
3.4. Peptide-αβIV-Tubulin Receptor Complex
3.5. Post-MM-GBSA Analysis
3.6. Physicochemical, Allergenicity, and Toxicity Prediction
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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DRAMP_ID | Sequence | Sequence Length |
---|---|---|
DRAMP00770 | GEYCGESCYLIPCFTPGCYCVSRQCVNKN | 29 |
DRAMP00775 | GIPCGESCVFIPCLTSAIDCSCKSKVCYRN | 30 |
DRAMP00776 | GSIPCEGSCVFIPCISAIIGCSCSNKVCYKN | 31 |
DRAMP00777 | GSIPCGESCVFIPCISAIIGCSCSSKVCYKN | 31 |
DRAMP00778 | GSIPCGESCVFIPCISAVIGCSCSNKVCYKN | 31 |
DRAMP00779 | GIPCGESCVFIPCISSVIGCSCSSKVCYRN | 30 |
DRAMP00780 | GSIPCGESCVFIPCISSVIGCACKSKVCYKN | 31 |
DRAMP00781 | GLPVCGETCVGGTCNTPGCGCSWPVCTRN | 29 |
DRAMP00782 | GLPVCGETCVGGTCNTPGCACSWPVCTRN | 29 |
DRAMP00783 | GIPCGESCVWIPCITSAIGCSCKSKVCYRN | 30 |
DRAMP00784 | GLPVCGETCVGGTCNTPGCSCSWPVCTRN | 29 |
DRAMP00788 | GLPICGETCVGGTCNTPGCSCSWPVCTRN | 29 |
DRAMP00789 | GVPICGETCTLGTCYTAGCSCSWPVCTRN | 29 |
Peptide ID | Global Energy (kcal/mol) | Attractive eVdW | Repulsive eVdW | ACE | HB | ClusPro Score |
---|---|---|---|---|---|---|
Peptide—αβI-tubulin receptor complex | ||||||
DRAMP00776 | −65.14 | −32.53 | 16.98 | −10.96 | −1.90 | −738.00 |
DRAMP00782 | −65.44 | −33.64 | 14.21 | −8.05 | −3.08 | −858.20 |
DRAMP00783 | −56.63 | −38.80 | 20.39 | −7.62 | −7.55 | −761.90 |
DRAMP00789 | −54.12 | −29.92 | −19.61 | −13.64 | −2.00 | −983.30 |
Peptide—αβII-tubulin receptor complex | ||||||
DRAMP00779 | −63.91 | −35.63 | 24.48 | −4.19 | −3.61 | −747.00 |
DRAMP00788 | −52.51 | −37.06 | 25.00 | −10.52 | −3.41 | −942.20 |
Peptide—αβIII-tubulin receptor complex | ||||||
DRAMP00776 | −43.38 | −29.11 | 10.37 | −4.88 | −3.59 | −736.40 |
DRAMP00781 | −32.08 | −22.85 | 10.24 | −6.45 | −1.65 | −735.60 |
Peptide—αβIV-tubulin receptor complex | ||||||
DRAMP00776 | −46.27 | −24.00 | 11.67 | −6.06 | −2.46 | −743.40 |
DRAMP00784 | −48.97 | −42.22 | 45.90 | −6.11 | −8.23 | −829.13 |
Before MD | After MD | ||||
---|---|---|---|---|---|
Residues | Distances (Å) | Interaction Types | Residues | Distances (Å) | Interaction Types |
DRAMP00776 | |||||
αAsp224 | 4.67 | Attractive charge | αAsp224 | 2.79 | Salt bridge |
αThr221, αArg359, βArg46, αGly223, βAsp355 | 2.17, 3.10, 3.04, 3.68, 3.63, | Conv–H and C–H bonds | αLys19, αAsn226, αArg276, αGln15 | 2.67, 3.29, 2.73, 3.00, 2.70 | Conv–H bond |
αHis227 | 3.30 | Pi–sigma | αGly71, αSer75, αGly79, αPro80, αGly223, αGlu22 | 3.46, 3.60, 3.15, 3.59, 3.45, 3.54, 3.80 | C–H bond |
αLys19 | 3.89 | Pi–cation; Pi–donor Hydrogen bond | |||
αLeu215, αArg276, βMet323 | 5.37, 4.61, 5.28 | Alkyl | |||
αHis227, αVal76, αLys19 | 4.87, 5.19, 4.86 | Pi-alkyl | |||
DRAMP00782 | |||||
αLys19 | 2.53457 | Salt bridge | αLys19 | 1.53 | Salt bridge; attractive charge |
βAsp41, βGlu45, αGlu22 | 4.52, 4.46, 4.99 | Attractive charge | βAsp41 | 2.78 | Attractive charge |
βAsp355, αLys19, αGly223 | 2.71, 3.35, 2.40 | Conv-H and C-H bonds | αGln15, αGly223, αSer25 | 1.67, 1.97, 1.81 | Conv–H bond |
βPro243, βLeu42 | 4.54, 4.94 | Alkyl | αLys19, αAsp31, αPro32, αThr221, αGly223 αGlu22 | 2.41, 2.77, 2.75, 2.83, 2.89, 2.43 | C–H bond |
βLeu42, αPro80 | 4.87, 4.75 | Alkyl | |||
DRAMP00783 | |||||
αSer78, αGly79, αTyr222, αGly223, αAsp224, βAsp355, αGln15, αSer75 αThr221, αSer78 αAsp224 | 2.89, 3.47, 2.18, 2.54, 3.21, 2.62, 3.15, 3.14, 2.32, 2.49, 3.11 | Conv–H and C–H bonds | αAsp224 βAsp41 | 1.77, 1.72, 1.58 | Salt bridge; attractive charge |
βLeu42 | 4.61255 | Alkyl | αAsp74, βAsp41, αAsp177 | 4.29, 5.25, 4.92, | Attractive charge |
αGln15, βAsp355, βGln245 | 2.39, 1.92, 1.68, 1.77, 2.48, 1.77, 1.69, 2.54, 1.93, 1.86 | Conv–H bond | |||
αAsp74 βAsp355 | 2.86, 2.65, 2.84, 2.87 | C–H bond | |||
βMet323, βVal353 | 5.20, 5.19 | Alkyl | |||
αTyr222 | 4.91 | Pi–alkyl | |||
DRAMP00789 | |||||
αGln279, βMet321, βMet323, αThr219, βAsp355, βGln245, αGly360, βSer322, βASP355 | 2.45, 3.03, 3.09, 2.90, 2.40, 3.13, 3.29, 3.25, 3.04, 3.41, | Conv-H and C–H bonds | αAsp26 | 2.70, 4.90 | Salt bridge/attractive charge |
βArg320 | 5.14 | Alkyl | αLys19, βMet323, αThr219, αAsp26, αArg282, αGly360 | 3.29, 3.25, 2.79, 2.63, 3.18, 3.05 | Conv–H bond |
αPro32, αSer275, αSer78, αSer78, αGly79 | 3.42, 3.78, 3.78, 3.45, 3.38 | C–H bond | |||
αPro32, αPro80, αArg359 | 4.88, 4.59, 4.87 | Alkyl |
Before MD | After MD | ||||
---|---|---|---|---|---|
Residues | Distances (Å) | Interaction Types | Residues | Distances (Å) | Interaction Types |
DRAMP00779 | |||||
βGlu45 | 2.61 | Salt bridge | βLys324, αAsp76, αGlu77, βAsp355 | 2.54, 2.65, 2.72, 2.7 | Salt bridge |
αArg221, αGlu279, βGlu45, αGlu77 | 4.35, 5.4, 5.08, 4.14 | Attractive charge | βAsp39, βAsp355 | 5.10, 4.87 | Attractive charge |
αThr82 βGly244 | 2.41, 2.51, 3.00 | Conv–H bond | αGly81, αArg221, βMet323, αGly81, αThr80, βAsp355 | 2.95, 3.00, 3.71, 2.89, 2.83, 2.81 | Conv–H bond |
αThr225, βGln245, αThr82, αGly365 | 3.32, 2.442, 3.06, 2.38 | C–H bond | |||
αArg229 | 3.32 | Pi–cation | αArg221, αGly365, βMet321 | 3.52, 3.79, 3.46 | C–H bond |
αTyr83, αAla19, αArg229 | 3.63, 4.03, 4.94 | Pi–alkyl | βPro243, βMet323, βLeu42 | 5.06, 5.20, 4.61, 5.31 | Alkyl |
DRAMP00788 | |||||
βAsp41 | 4.44 | Attractive charge | αGlu279, αAsp218 | 1.63, 1.51 | Salt bridge; attractive Charge |
αArg221 | 2.90 | Conv–H bond | βAsn247, βVal353, βAsp355, αThr73, βVal353, αGlu22, αThr82 | 2.01, 2.74, 2.47, 2.50, 2.52, 1.64, 1.98 | Conv–H bond |
βLeu246, βAsp41 | 2.41, 3.42 | C–H bond C–H bond | αThr82, Ser178, αSer178, αPro364, βGly244, βGln245, βAla352, αLeu217, βleu246, αVal177, βGln245 | 2.53, 2.71, 3.09, 2.27, 2.75, 2.79, 2.41, 3.02, 2.40, 2.50, 2.57, 2.63 | C–H bond |
αThr225 | 3.44, 3.30 | Pi–donor | αThr225 | 2.65 | Pi–donor hydrogen bond |
αTyr224 | 5.23, 3.85 | Pi–alkyl | αIle219, αLeu217, αPro364, αPro364 | 5.18, 5.14, 4.63, 4.92 | Alkyl |
Residues | Distances (Å) | Interaction Types | Residues | Distances (Å) | Interaction Types |
---|---|---|---|---|---|
DRAMP00776 | |||||
αGlu22 | 4.63 | Attractive charge | αGlu22 | 4.67 | Attractive charge |
αThr82, αArg229, βGly244, βLeu246 | 3.22, 2.37, 2.76, 3.16 | Conv–H bond | αGln11, αThr82, βGln245 βGly244, αGlu77, αGln15, αGln15, αGly366 | 1.91, 2.60, 2.17, 1.98, 1.89, 3.09, 2.87, 2.10, 2.53, 2.08 | Conv–H bond |
αAsn18, αGlu22, αThr82 | 3.21, 2.37, 3.28 | C–H bond | αGly81, αThr225, αArg229, βGly244, αGln15, αGly365, αGly366 | 2.68, 2.56, 2.36, 2.65, 2.53, 2.74, 2.88, 2.61 | C–H bond |
βPro243 | 5.10 | Alkyl | βMet323, αVal74 | 4.81, 5.12 | Alkyl |
αTyr224 | 4.76 | Pi–alkyl | αTyr224 | 4.41 | Pi–alkyl |
DRAMP00781 | |||||
αThr225, αArg229, αGlu22 | 2.32, 2.59, 2.79, 3.08 | Conv–H bond | αGln15, αTyr83, βArg46, βGly244, αThr82, αGlu22, αGln15, αVal74, αThr73, αGlu77, αGly29, αIle30 | 1.93, 1.81, 2.94, 1.89, 2.71, 2.50, 1.81, 1.67, 2.93, 2.89, 1.89, 1.91, 2.81, 2.67 | Conv–H bond |
αGlu22, αThr225, αGln11, βGly244, βLeu246 | 2.32, 2.88, 3.62, 2.27, 3.56 | C–H bond | αPro32, αThr82, αGlu22, αThr73, βGln245, αGlu77 | 2.79, 2.73, 2.76, 2.68, 2.92, 2.98 | C–H bond |
αPro364 | 3.73, 4.39 | Alkyl | αVal363, αPro364, αPro364, αPro32, αLeu26, βLeu42, βPro243 | 4.51, 4.70, 5.08, 5.30, 4.69, 4.71, 4.76 | Alkyl |
αTyr224 | 3.83 | Pi–alkyl |
Residues | Distances (Å) | Interaction Types | Residues | Distances (Å) | Interaction Types |
---|---|---|---|---|---|
DRAMP00776 | |||||
αGlu113, βGlu125 | 5.19, 4.55 | Attractive charge | βGlu125 | 1.73 | Salt bridge; attractive charge |
βGlu125 | 2.44, 3.02 | Conv–H bond | αGly95, βGlu125, βAsp128 | 2.32, 2.83, 3.09 | Conv–H bond |
αLys96, βSer126 | 3.20, 2.32, 3.02 | C–H bond | αThr109, βPhe159, βPro160, αThr94, αGly95, βAsp128, βCys127 | 2.95, 2.65, 2.45, 2.56, 2.57, 2.81, 2.74, 2.95, 2.45, 2.38 | C–H bond |
βGlu158, βAsp161 | 4.49, 4.20 | Pi–anion | βArg162 | 4.73, | Pi–cation |
DRAMP00784 | |||||
αGln31, αThr82, αAsn228, αArg229, βGly244, αGlu22 | 2.00, 2.30, 2.88, 1.88, 2.45, 2.65, 2.61, 1.93, 2.34 | Conv–H bond | αAsp76 | 4.89 | Attractive charge |
αThr82, αThr225, αGln15, βGly244, βGln245 | 2.47, 2.83, 2.68, 2.48, 2.65, 2.83, 2.85, 2.53, 2.58, 2.54 | C–H bond | αGlu77, αAsn228, αGln15, αThr73, αAsn18, βAsp41 | 3.54, 3.31, 2.81, 3.00, 3.04, 3.00 | Conv–H bond |
αPro32 | 4.97 | Alkyl | βLeu246 | 5.07 | Alkyl |
αTyr83 | 5.11 | Pi–alkyl | αTyr224 | 4.44 | Pi–alkyl |
Physicochemical Properties | Toxicity | Allergenicity | |||||||
---|---|---|---|---|---|---|---|---|---|
Peptide ID | Aliphatic Index | Instability Index | Theoretical pl | Total Number of Negatively Charge Residues (Asp + Glu) | Total Number of Negatively Charge Residues (Asp + Glu) | Total Number of Atoms | Mol wt | Prediction | AllerTOP v. 2.0 |
DRAMP00776 | 84.84 | 26.45 | 7.77 | 1 | 2 | 437 | 3197.24 | Non-toxin | Probable non-allergen |
DRAMP00779 | 81.00 | 31.50 | 7.77 | 1 | 2 | 423 | 3113.1 | Non-toxin | Probable allergen |
DRAMP00781 | 0.162 | 35.35 | 5.92 | 1 | 1 | 378 | 2872.71 | Non-toxin | Probable non-allergen |
DRAMP00782 | 46.90 | 50.50 | 5.96 | 1 | 1 | 381 | 2886.73 | Non-toxin | Probable non-allergen |
DRAMP00783 | 74.67 | 18.66 | 8.33 | 1 | 3 | 434 | 3179.21 | Non-toxin | Probable allergen |
DRAMP00784 | 43.45 | 46.59 | 5.96 | 1 | 1 | 382 | 2902.32 | Non-toxin | Probable non-allergen |
DRAMP00788 | 46.90 | 39.95 | 5.96 | 1 | 1 | 385 | 2916.76 | Non-toxin | Probable non-allergen |
DRAMP00789 | 50.34 | 52.46 | 5.96 | 1 | 1 | 395 | 2983.84 | Non-toxin | Probable non-allergen |
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Ebenezer, O.; Damoyi, N.; Shapi, M.; Wong, G.K.-S.; Tuszynski, J.A. A Molecular Docking Study Reveals That Short Peptides Induce Conformational Changes in the Structure of Human Tubulin Isotypes αβI, αβII, αβIII and αβIV. J. Funct. Biomater. 2023, 14, 135. https://doi.org/10.3390/jfb14030135
Ebenezer O, Damoyi N, Shapi M, Wong GK-S, Tuszynski JA. A Molecular Docking Study Reveals That Short Peptides Induce Conformational Changes in the Structure of Human Tubulin Isotypes αβI, αβII, αβIII and αβIV. Journal of Functional Biomaterials. 2023; 14(3):135. https://doi.org/10.3390/jfb14030135
Chicago/Turabian StyleEbenezer, Oluwakemi, Nkululeko Damoyi, Michael Shapi, Gane Ka-Shu Wong, and Jack A. Tuszynski. 2023. "A Molecular Docking Study Reveals That Short Peptides Induce Conformational Changes in the Structure of Human Tubulin Isotypes αβI, αβII, αβIII and αβIV" Journal of Functional Biomaterials 14, no. 3: 135. https://doi.org/10.3390/jfb14030135