Comparative study of the interactions between C60 fullerene and SARS-CoV-2, HIV, eukaryotic, and bacterial model membranes: Insights into antimicrobial strategies with C60-peptide hybrids.

The neutrophil-derived peptide, indolicidin, and the sphere-shaped carbon nanoparticle, C60, are contemporary components capable of acting as bactericides and virucides, among others. Herein, the coarse-grained molecular dynamics simulation method was used to simulate the interactions of gram-negative bacteria, eukaryotes, human immunodeficiency virus (HIV), and SARS-COV-2 membrane models with indolicidin, C60s, and C60-indolicidin hybrids. Our results demonstrated that the carbon nanoparticle penetrated all membrane models, except the bacterial membrane, which remained impenetrable to both the peptide and C60. Additionally, the membrane thickness did not change significantly. The peptide floated above the membranes, with only the side chains of the tryptophan (Trp)-rich site slightly permeating the membranes. After achieving stable contact between the membrane models and nanoparticles, the infiltrated C60s interacted with the unsaturated tail of phospholipids. The density results showed that C60s stayed close to indolicidin and continued to interact with it even after penetration. Indolicidin, especially its Trp-rich site, exhibited more contact with the head and tail of neutral phospholipids compared to other phospholipids. Moreover, both particles interacted with different kinds of glycosphingolipids located in the eukaryote membrane. This investigation has the potential to advance our knowledge of novel approaches to combat antimicrobial resistance.

Chemical Modification of the Amino Groups of Human Insulin: Investigating Structural Properties and Amorphous Aggregation of Acetylated Species.

The efficacy of human recombinant insulin can be affected by its aggregation. Effects of acetylation were observed on insulin structure, stability, and aggregation at 37 and 50 °C and pH of 5.0 and 7.4 with the use of spectroscopy, circular dichroism (CD), dynamic light scattering (DLS), and atomic force microscopy (AFM). Raman and FTIR results were indicative of structural changes in AC-INS, and CD analyses showed a slight increase in ß-sheet content in AC-INS. Melting temperature (Tm) measurements indicated an overall more stable structure and spectroscopic assessment showed a more compact one. Formation of amorphous aggregates was followed over time and kinetics parameters showed a longer nucleation phase (higher t* amount) and lower aggregates amount (lower Alim) for acetylated insulin (AC-INS) compared to native (N-INS) in all tested conditions. The results of amyloid-specific probes approved the formation of amorphous aggregates. Size particle and microscopic analysis suggested that AC-INS was less prone to form aggregates, which were smaller if formed. In conclusion, this study has demonstrated that controlled acetylation of insulin may lead to its higher stability and lower propensity toward amorphous aggregation and has provided insight into the result of this type of post-translational protein modification.

A Survey of Gasoline Ameliorator, Methyl-Tert-Butyl Ether (MTBE) on Bovine Serum Albumin: A Spectroscopy and Molecular Dynamic Simulation Study.

Background: Methyl-Tert-Butyl Ether (MTBE) as a gasoline modifier is frequently added to fuels and used in plenty of worldwide applications. MTBE biodegradation in groundwater occurs slowly and produces water miscibility; therefore, it causes diverse environmental and human health concerns. Objectives: The interaction of MTBE with bovine serum albumin (BSA) as a model protein at physiological conditions is investigated to illustrate the possible interactions of MTBE with the body's proteins. Materials and Methods: Uv-visible, fluorescence, circular dichroism (CD) spectroscopy methods, and molecular modeling were used to analyze the MTBE's effect on BSA structure and dynamics. The constant protein concentration and various MTBE contents were used for possible interactions. Results: The protein structural analysis shows that MTBE binds to BSA via positive enthalpy and entropy via hydrophobic interactions. Molecular docking shows the participation of several amino acids in the MTBE-BSA interaction. The CD spectroscopy results show that the BSA structure was not changed in the MTBE concentrations utilized in the study. Molecular dynamics (MD) simulation results suggest that MTBE can slightly change protein structure in the last 50ns. Conclusion: Comparing experimental and MD simulation results demonstrated that the BSA secondary structure was maintained in the low concentration of the MTBE. The entropy and enthalpy parameters asserted the hydrophobic interaction was the major force in the interaction between the BSA and MTBE.

Atomistic insight into the luminal allosteric regulation of vesicular glutamate transporter 2 by chloride and protons: An all-atom molecular dynamics simulation study.

Vesicular glutamate transporters (VGLUTs) are essential components of synaptic transmission in the brain. Synaptic vesicles' luminal chloride and low pH regulate VGLUTs allosterically in a cooperative way. The luminal allosteric regulation of VGLUTs by chloride (Cl- ) and proton (H+ ) is possible through the collective work of luminal Cl- and H+ binding site residues. However, precise atomistic details about the luminal Cl- binding to the luminal Cl- binding site and the role of allosteric activation by H+ in VGLUTs are unknown. Using all-atom molecular dynamics simulations, this study demonstrates the critical role of Cl- binding site residues, details about Cl- binding to the luminal Cl- binding site, and the role of allosteric regulation of VGLUT2 by H+ at an atomistic level. By point mutations, we found out that Arginine (R184), Histidine (H128), and Glutamate (E191) are critical residues in the allosteric regulation of VGLUT2, R184 is the luminal Cl- binding site residue, and H128 and R88 support Cl- binding to R184. Furthermore, we found out that the protonation of H128 and E191 is important in Cl- binding to the luminal Cl- binding site. Furthermore, we investigated the essential interactions between Cl- and H+ binding site residues. Our results can give atomistic evidence for a previous experimental hypothesis about the VGLUTs luminal allosteric regulation by H+ and Cl- .

Molecular insights into the crystalline nanocellulose and human lysozyme interactions: An experimental and theoretical research.

In the present research, we performed a combination of detailed computational and spectroscopic methods to determine the effect of crystalline nanocellulose (CNC) on the structure and dynamics of human lysozyme (hLyz). Fluorescence spectroscopy revealed static quenching as the major mechanism in forming a stable CNC-hLyz complex, and the binding was energetically favorable. The obtained values of the thermodynamic parameters (∆G, ∆H, and ∆S) proposed that the complex formation between the enzyme and cellulose nanocrystals is driven by electrostatic interactions, which were also confirmed by molecular dynamics (MD) simulation. Additionally, the MD simulation analysis displays that the enzyme's structural elements and tertiary structure were primarily maintained, and only loops regions were affected in the presence of cellulose nanocrystals. At the same time, circular dichroism (CD) outcomes highlighted that higher cellulose nanocrystals concentration caused a reduction in the secondary structure of hLyz. Our observations proved that low cellulose nanocrystals concentrations have no considerable effect on the human lysozyme structure. The current research results provide a valuable opportunity to elucidate the molecular interactions between protein and nanocelluloses, guiding further investigations of CNC-based material for biomedical, pharmaceutical, and food industry applications.

Design and synthesis of polyacrylic acid/deoxycholic acid-modified chitosan copolymer and a close inspection of human growth hormone-copolymer interactions: An experimental and computational study.

Despite efforts to achieve a long-acting formulation for human growth hormone (hGH), daily injections are still prescribed for children with growth hormone deficiency. To grapple with the issue, acquiring a deep knowledge of the protein and understanding its interaction mechanism with the carrier can be beneficial. Herein, we designed and synthesized a novel chitosan-based copolymer and investigated its interaction with hGH using a combination of experimental and computational strategies. To construct the amphiphilic triblock copolymers (CDP), we grafted deoxycholic acid (DCA) and polyacrylic acid (PAA) onto the chitosan chains, and Fourier-transform infrared (FTIR) analysis confirmed the proper formation of CDP. Circular dichroism (CD) demonstrated the preservation of the secondary structure of hGH interacting with CDP, and, further, fluorescence spectroscopy proved the stability of the tertiary structure of the protein. Applying molecular dynamics simulation (MD), we examined the dynamics and integrity of hGH in the presence of the copolymer and compared its behavior with the protein in aquatic environments. Additionally, energy and contact analysis illustrated that the residues involved in the interaction were located predominantly in the connecting loops, and van der Waals (vdW) and electrostatic interactions were the main driving forces of the polymer-protein complex formation. This research's main aim was to trace the protein-polymer interaction's mechanism. We anticipate that the utility of the copolymer can address the challenges of fabricating a new sustained-release delivery platform for therapeutic proteins.

Molecular Insights into Pore Formation Mechanism, Membrane Perturbation, and Water Permeation by the Antimicrobial Peptide Pleurocidin: A Combined All-Atom and Coarse-Grained Molecular Dynamics Simulation Study.

The antimicrobial peptide (AMP) pleurocidin has a broad antimicrobial activity against Gram-negative and Gram-positive bacteria by perturbation and permeabilizing their membranes; however, understanding the mechanism of action of pleurocidin, a promising AMP for replacing current antibiotic agents, has tremendous importance for future applications. Hence, we applied all-atom (AA) and coarse-grained (CG) molecular dynamics (MD) simulations to provide molecular-level insights into the pore-forming process. The early stages of pore formation were examined by 500 ns AA simulations. The results demonstrated that pleurocidin has the ability to create a pore with two peptides through which water molecules can flow. However, the results of the 25 µs CG simulations indicate that the final pore will be created by accumulation of more than two peptides. The results show that after 2.5 µs of simulations, peptides will aggregate and create a channel-like pore across the membrane. Pleurocidin can construct a more efficient and stable pore in the anionic membranes than in the zwitterionic membranes. Moreover, the structure amphipathicity, polarity, and basic residues play crucial roles in the pore formation and flow of water molecules across the lipid bilayers. In general, the findings revealed that based on the lipid compositions of the membranes, pleurocidin could act by forming either toroidal or disordered toroidal pores with different peptide arrangements.

Effect of the Met148Leu mutation on the structure and dynamics of the rusticyanin protein from Acidithiobacillus sp. FJ2.

The rusticyanin protein, a blue monomeric copper protein type-1, is one of the main components in the iron-electron transfer chain of the Acidithiobacillus ferrooxidans, and is the product of the rus gene expression. Herein, first the bacterial DNA of Acidithiobacillus sp. FJ2 was extracted. Then, the rus gene sequence and the sequence amino acid rusticyanin protein were determined. The Met148Leu mutation increased the oxidase activity of the rusticyanin protein, thereby enhancing the efficiency of the bioleaching process by bacteria Acidithiobacillus ferroxidans. Met148Leu mutation was created in the rusticyanin protein, then molecular dynamics (MD) simulations and structural analysis were performed. The MD analysis of the wild-type and mutant protein demonstrated a slight instability in the mutant protein and significant instability in the active site of the mutant protein. The usefulness of this study is the genetic manipulation of the native Acidithiobacillus sp. FJ2 bacterium, which can boost the bioleaching efficiency of the bacterium to some extent, and investigating its effects on the structure of a mutant protein using computational methods.

Refinement of coding SNPs in the human aryl hydrocarbon receptor gene using ISNPranker: An integrative-SNP ranking web-tool.

Different bioinformatic methods apply various approaches to predict how much the effect of a SNP could be deleterious and therefore their results may differ significantly. However, variation studies often need to consider an integrated prediction result to analyze the effect of SNPs. To address this problem, we used an algorithm to map ordinal predictions to a numeral space and averaging them, and based on it we developed the ISNPranker web-tool (http://isnpranker.semilab.ir/). It takes heterogonous outputs of different predictors and generates integrated numerical predictions and ranks SNPs based on them. Afterward, we used ISNPranker to identify the most deleterious coding SNPs (cSNPs) of the human aryl hydrocarbon receptor (AHR) gene. AHR is a ligand-activated transcription factor that governs many molecular and cellular mechanisms and cSNPs may affect its structure, interactions, and function. Forty validated cSNPs of AHR were initially analyzed using 16 publicly available SNP analyzers and the results were introduced to the ISNPranker and integrated predictions were obtained. The cSNPs were ranked in 34 levels of danger and rs200257782 in the ARNT dimerization domain (ADD121-289) of AHR was identified as the most deleterious cSNP. The rs148360742, which affect ADD40-79 and Hsp90 binding domain (HBD27-79) was in the second rank and the third and fourth ranks were occupied by ADD121-289-located variations rs571123681 and rs141667112 respectively. In conclusion, we introduced ISNPranker, which is a web-tool for integrative ranking of SNPs, and we showed that AHR structure and function may be highly sensitive to the cSNPs in the ARNT dimerization domain.

Insight into the Microcosm of the Human Growth Hormone and Its Interactions with Polymers and Copolymers: A Molecular Dynamics Perspective.

Therapeutic proteins nowadays have increasingly been applied for their considerable potential in treating a wide variety of diseases. The effectiveness and potency of native therapeutic proteins are limited by various factors (e.g., stability, blood circulation time, specificity). Over the past years, a great deal of effort has been devoted to developing safe and efficient protein delivery systems. Entrapment of protein into polymeric and copolymeric matrices is common among the different types of protein-based drug formulation. However, despite the massive efforts toward developing therapeutic protein delivery in experimental studies and industrial applications, there is relatively little data on the influence of polymers and copolymers on therapeutic proteins at the atomic and molecular levels. Herein, molecular dynamics (MD) simulations are used to study the effects of biocompatible synthetic polymers including methoxy poly(ethylene glycol) (MPEG), poly(lactic acid) (PLA), and poly(lactic acid) copolymers (poly(lactic-co-glycolic acid)) PLGA and MPEG-PLA(PELA)) on the structure and dynamics of the human growth hormone (hGH), and the results are compared with previous experimental findings. Our results indicate that the hGH conformation remains stable both in pure water and in the presence of polymers, and these results are in good agreement with previous experimental data. It is shown that the MPEG chains are self-assembled and folded into a semicrystalline structure; therefore, only a small portion of the protein interacts with the polymer. The other three polymers, however, interact well with the protein and partially cover its surface. Our findings suggest that the use of these polymers for protein encapsulation has the advantage of reducing protein aggregation and thus increasing drug serum half-life. Eventually, we anticipate that the research results will expand the current knowledge about encapsulation mechanisms and the molecular interactions between hGH and the polymers.

Molecular Insight into the Interaction between Camptothecin and Acyclic Cucurbit[4]urils as Efficient Nanocontainers in Comparison with Cucurbit[7]uril: Molecular Docking and Molecular Dynamics Simulation.

Cucurbit[n]urils (CB[n], n = 5, 6, 7, 8, 10, 14) and their derivatives due to the hydrophobic cavities and polar carbonyl portals have been considerably explored for their potential uses as drug delivery systems. It is important to understand how these macrocyclic compounds interact with guests. Camptothecin (CPT), as a natural alkaloid, is a topoisomerase inhibitor with antitumor activity against breast, pancreas, and lung cancers. The application of this drug in cancer therapy is restricted due to its low aqueous solubility and high toxicity. Recently, the complex formation between the cucurbit[7]uril (CB[7])/acyclic cucurbit[4]uril (aCB[4]) nanocontainers and CPT have been evaluated to overcome the potential drawbacks of the related drug. Herein, using computational methods, we identified the interaction mechanism of CPT with CB[7]/aCB[4]s, which consist of benzene and naphthalene sidewalls (aCB[4]benzene and aCB[4]naphthalene, respectively) since the experimental approaches have not completely provided information at the molecular level. Our molecular docking and molecular dynamics (MD) simulations show that CB[7] and its two acyclic derivatives form stable inclusion complexes with CPT especially through hydrophobic interactions. We also found that aCB[4]s with the aromatic sidewalls can attach to CPT through π-π interactions. This investigation highlights aCB[4]s due to the structural properties and flexible nature as better nanocontainers for controlled release delivery of pharmaceutical agents in comparison with the CB[7] nanocontainer.

Structural Studies on an Anti-Angiogenic Peptide Using Molecular Modeling.

BACKGROUND: Development of VEGF antagonists, which inhibit its interaction with the receptors, is a widely used strategy for the inhibition of angiogenesis and tumor growth. OBJECTIVES: In the present study, a VEGFR-1 antagonistic peptide was designed and its potential for binding to VEGFR-1 and VEGFR-2 was evaluated by theoretical studies. MATERIALS AND METHODS: Based on the X-ray structure of VEGF-B/VEGFR-1 D2 (PDB ID: 2XAC), an antagonistic peptide (known as VGB1) was designed, and its model structure was constructed using homology modeling in the MODELLER, version 9.16. The validity of the modeled structures was estimated employing several web tools. Finally, one model was chosen and molecular dynamics (MD) simulation was applied using the GROMACS package, version 5.1.4, to allow conformational relaxation of the structure. Next, docking process of the peptide with VEGFR-1 and VEGFR-2 was performed by HADDOCK web server and the docking structures were optimized by MD simulation for 20 ns. The far-UV circular dichroism (CD) spectrum of VGB1 was recorded to evaluate the overall structure of the peptide. RESULTS: The far-UV CD spectrum indicated that VGB1 contains α helix structure. The results from docking studies suggested that Van der Waals and nonpolar interactions play the most important role in the peptide binding to VEGFR-1. In addition, our results implicated the relevance of both Van der Waals and electrostatic interactions in the formation of complex between VGB1 and VEGFR-2. In addition to the common binding residues in the corresponding region of VEGF-A and VEGF-B, additional binding residues also were predicted for the interaction of VGB1 with VEGFR-1 and VEGFR-2. CONCLUSIONS: The results of MD and molecular docking simulations predicted that VGB1 recognizes both VEGFR-1 and VEGFR-2, which may lead to the prevention of the downstream signaling triggered by these receptors.

Encapsulation of an endostatin peptide in liposomes: Stability, release, and cytotoxicity study.

The endostatin protein is a potent inhibitor of angiogenesis and tumor growth. The anti-angiogenic and antitumor properties of full-length endostatin can be mimicked by its N-terminal segment, including residues 1-27. Therefore, our previous studies have shown that a mutant N-terminal peptide which the Zn-binding loop was replaced by a disulfide loop (referred to as the ES-SS peptide) has preserved antiangiogenic and antitumor properties compared to the native peptide. To increase stability and plasma half-life of the ES-SS peptide, the nano-sized liposomal formulations of the peptide with different ratio of phosphocholine (PC) were synthesized. The liposomal peptide formulations possessed an average size of around 100 nm with (-4 to -36 mv) in zeta potential. The encapsulation efficiency of the ES-SS peptide was in the range of 24-54% with different lipid: peptide molar ratios. In vitro release of the peptide from liposomes indicated a complete peptide release after 7 days. Cytotoxicity assay was evaluated using the human umbilical vein endothelial cells (HUVECs) for various concentrations of the liposomal peptide. The results depicted the gradual release of the peptide through liposomes. By comparing with the free peptide, the liposomal peptide formulations have indicated higher cell viability with IC50 value about 0.1 µM. The peptide-liposome interactions, as well as the peptide effect on the liposome structure, were also investigated through coarse-grained molecular dynamics (CG-MD) simulation. The results revealed that the peptides were assembled in the hydrophilic core of the liposome. The peptide behavior in liposome can stabilize the liposome structure and be a response to the observed low peptide release rate. The investigation is promising for designing a liposome-based anti-angiogenesis peptide delivery system.

Molecular Basis for Membrane Selectivity of Antimicrobial Peptide Pleurocidin in the Presence of Different Eukaryotic and Prokaryotic Model Membranes.

Pleurocidin, a 25-residue cationic peptide, has antimicrobial activity against bacteria and fungi but exhibits very low hemolytic activity against human red blood cells (RBC). The peptide inserts into the bacterial membrane and causes the membrane to become permeable by either toroidal or carpet mechanism. Herein, to investigate the molecular basis for membrane selectivity of Pleurocidin, the interaction of the peptide with the different membrane models including the RBC, DOPC, DOPC/DOPG (3:1), POPE/POPG (3:1), and POPE/POPG (1:3) bilayers were studied by performing all-atom molecular dynamics (MD) simulation. The MD results indicated that the peptide interacted weakly with the neutral phospholipid bilayers (DOPC), whereas it made strong interactions with the negatively charged phospholipids. Pleurocidin maintained its α-helical structure during interactions with the anionic model membranes, but the peptide lost its secondary structure adjacent to the neutral model membranes. The results also revealed that the Trp-2, Phe-5, and Phe-6 residues, located in the N-terminal region of the peptide, played major roles in the insertion of the peptide into the model membranes. In addition, the peptide deeply inserted into the DOPC/DOPG membrane. The order analysis showed that Pleurocidin affected the order of anionic phospholipids more than zwitterionic phospholipids. The cholesterol molecules help the RBC membrane conserve integrity in response to Pleurocidin. This research has provided data on the Pleurocidin-membrane interactions and the reasons of resistance of eukaryotic membrane to the Pleurocidin at atomic details that are useful to develop potent AMPs targeting multidrug-resistant bacteria.

Paclitaxel interaction with cucurbit [7]uril and acyclic Cucurbit[4]uril nanocontainers: A computational approach.

Paclitaxel (PTX) is a natural terpenoid compound that has been broadly studied for its antitumor activities and widely used as a chemotherapy medication. The treatment efficacy of PTX is affected by its low aqueous solubility, thus causing a subject of extensive research. In recent years, synthetic molecular containers such as cucurbit[n]urils (CB[n]s) and their derivatives have been significantly developing because of their remarkable ability to bind hydrophobic and cationic drugs. Recent experimental studies have shown that acyclic CB[n]-type containers (aCB[n]s), as new derivatives of the family of CB[n]s, increase the solubility of insoluble pharmaceuticals. However, the nature by which the drug interacts with carriers remains largely unknown. In this study, molecular docking and molecular dynamics (MD) simulation were performed to understand how CB[7] and aCB[4] nanocontainers interact with PTX which affect its aqueous solubility. The results clarify how the flexibility of containers is influenced by their structure and how this affects their interactions with PTX. Our results reveal that although both CB[7] and aCB[4] are capable of binding to PTX, the affinity to aCB[4] is higher than that of CB[7]. It has also been shown that the binding to both CB[7] and aCB[4] is probably an entropy-driven process. This research supports the potential use of the cucurbit[n]urils and their acyclic derivatives as drug delivery systems.

A cyclic peptide reproducing the α1 helix of VEGF-B binds to VEGFR-1 and VEGFR-2 and inhibits angiogenesis and tumor growth.

Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are pivotal regulators of angiogenesis. The VEGF-VEGFR system is therefore an important target of anti-angiogenesis therapy. Based on the X-ray structure of VEGF-B/VEGFR-1 D2, we designed a cyclic peptide (known as VGB1) reproducing the α1 helix and its adjacent region to interfere with signaling through VEGFR-1. Unexpectedly, VGB1 bound VEGFR-2 in addition to VEGFR-1, leading to inhibition of VEGF-stimulated proliferation of human umbilical vein endothelial cells and 4T1 murine mammary carcinoma cells, which express VGEFR-1 and VEGFR-2, and U87 glioblastoma cells that mostly express VEGFR-2. VGB1 inhibited different aspects of angiogenesis, including proliferation, migration and tube formation of endothelial cells stimulated by VEGF-A through suppression of extracellular signal-regulated kinase 1/2 and AKT (Protein Kinase B) phosphorylation. In a murine 4T1 mammary carcinoma model, VGB1 caused regression of tumors without causing weight loss in association with impaired cell proliferation (decreased Ki67 expression) and angiogenesis (decreased CD31 and CD34 expression), and apoptosis induction (increased TUNEL staining and p53 expression, and decreased Bcl-2 expression). According to far-UV circular dichroism (CD) and molecular dynamic simulation data, VGB1 can adopt a helical structure. These results, for the first time, demonstrate that α1 helix region of VEGF-B recognizes both VEGFR-1 and VEGFR-2.

The role of intermolecular interactions on the encapsulation of human insulin into the chitosan and cholesterol-grafted chitosan polymers.

Chitosan and its derivatives used in drug delivery investigations could contribute to improving peptide and protein drug delivery systems. Herein, the molecular dynamics (MD) simulation approach was applied to evaluate the important driving factors of the human insulin encapsulation into the chitosan and cholesterol-modified chitosan polymers. The MD results revealed that the native conformation of insulin was stabilized by the chitosan polymers. In the present study, the effect of cholesterol moieties of modified chitosan was also examined and the results indicated that the cholesterol components would decrease the tendency of chitosan polymers to human insulin. Further analyses showed that the intermolecular interactions between the tyrosine, phenylalanine, and acidic residues are important in the formation of the insulin-polymer complexes. Another interesting finding was that the van der Waals, electrostatic, and CH-π interactions play key roles in the encapsulation process. Generally, in the case of human insulin, the MD simulation results would seem to suggest that the chitosan nanoparticles could be the more suitable carrier than the cholesterol-grafted chitosan nanoparticles.

Molecular Self-Assembly Strategy for Encapsulation of an Amphipathic α-Helical Antimicrobial Peptide into the Different Polymeric and Copolymeric Nanoparticles.

Encapsulation of peptide and protein-based drugs in polymeric nanoparticles is one of the fundamental fields in controlled-release drug delivery systems. The molecular mechanisms of absorption of peptides to the polymeric nanoparticles are still unknown, and there is no precise molecular data on the encapsulation process of peptide and protein-based drugs. Herein, the self-assembly of different polymers and block copolymers with combinations of the various molecular weight of blocks and the effects of resultant polymer and copolymer nanomicelles on the stability of magainin2, an α-helical antimicrobial peptide, were investigated by means of all-atom molecular dynamics (MD) simulation. The micelle forming, morphology of micellar aggregations and changes in the first hydration shell of the micelles during micelles formation were explored as well. The results showed that the peptide binds to the polymer and copolymer micelles and never detaches during the MD simulation time. In general, all polymers and copolymers simultaneously encapsulated the peptide during micelles formation and had the ability to maintain the helical structure of the peptide, whereas the first hydration shell of the peptide remained unchanged. Among the micelles, the polyethylene glycol (PEG) micelles completely encapsulated magainin2 and, surprisingly, the NMR structure of the peptide was perfectly kept during the encapsulation process. The MD results also indicated that the aromatic and basic residues of the peptide strongly interact with polymers/copolymers and play important roles in the encapsulation mechanism. This research will provide a good opportunity in the design of polymer surfaces for drug delivery applications such as controlled-release peptide delivery systems.