Relationship between Protein-Induced Membrane Curvature and Membrane Thermal Undulation.

This work studied the membrane curvature generated by anchored proteins lacking amphipathic helices and intrinsic morphologies, including the Epsin N-terminal homology domain, intrinsically disordered C-terminal domain, and truncated C-terminal fragments, by using coarse-grained molecular dynamics simulations. We found that anchored proteins can stabilize the thermal undulation of membranes at a wavelength five times the protein's binding size. This proportional connection is governed by the membrane bending rigidity and protein density. Extended intrinsically disordered proteins with relatively high hydrophobicity favor colliding with the membrane, leading to a much larger binding size, and show superiority in generating membrane curvature at low density over folded proteins.

Structural and thermodynamic properties of bulk triglycerides and triglyceride/water mixtures reproduced using a polarizable coarse-grained model.

Triglycerides (TGs) play important roles in renewable energies, food production, medicine, and metabolism in organisms. Here, we developed a novel coarse-grained (CG) force field (FF) for triglycerides to reproduce both the structural and thermodynamic properties of bulk TGs, TG/air interfaces, and TG/water mixtures using molecular dynamics (MD) simulations. We rigorously optimized the bonded and nonbonded force parameters between the CG beads of TGs and nonbonded force parameters between TG beads and polarizable CG water beads by employing an efficient meta-multilinear interpolation parameterization algorithm recently developed by us. This CG FF performs very well in reproducing the percolating network of the TG bulk phase self-assembled in water and a variety of molecular conformations predicted by all-atom MD simulations. More importantly, it also correctly reproduces multiple experimentally measurable macroscopic thermodynamic properties, including the density and surface tensions of both the TG/air and TG/water interfaces. This paves the way for studying more complicated systems involving TGs on a large scale.

How Alligator Immune Peptides Kill Gram-Negative Bacteria: A Lipid-Scrambling, Squeezing, and Extracting Mechanism Revealed by Theoretical Simulations.

Alligator sinensis cathelicidins (As-CATHs) are antimicrobial peptides extracted from alligators that enable alligators to cope with diseases caused by bacterial infections. This study assessed the damaging effects of sequence-truncated and residue-substituted variants of As-CATH4, AS4-1, AS4-5, and AS4-9 (with decreasing charges but increasing hydrophobicity) on the membranes of Gram-negative bacteria at the molecular level by using coarse-grained molecular dynamics simulations. The simulations predicted that all the variants disrupt the structures of the inner membrane of Gram-negative bacteria, with AS4-9 having the highest antibacterial activity that is able to squeeze the membrane and extract lipids from the membrane. However, none of them can disrupt the structure of asymmetric outer membrane of Gram-negative bacteria, which is composed of lipopolysaccharides in the outer leaflet and phospholipids in the inner leaflet. Nonetheless, the adsorption of AS4-9 induces lipid scrambling in the membrane by lowering the free energy of a phospholipid flipping from the inner leaflet up to the outer leaflet. Upon binding onto the lipid-scrambled outer membrane, AS4-9s are predicted to squeeze and extract phospholipids from the membrane, AS4-5s have a weak pull-out effect, and AS4-1s mainly stay free in water without any lipid-extracting function. These findings provide inspiration for the development of potent therapeutic agents targeting bacteria.

LncRNA model predicts liver cancer drug resistance and validate in vitro experiments.

Introduction: Hepatocellular carcinoma (HCC) patients may benefit from chemotherapy, but drug resistance is an important obstacle to favorable prognoses. Overcoming drug resistance is an urgent problem to be solved. Methods: Differential expression analysis was used to identify long non-coding RNAs (LncRNAs) that differed in chemotherapy-sensitive and chemotherapy-resistant patients. Machine learning algorithms including random forest (RF), lasso regression (LR), and support vector machines (SVMs) were used to identify important chemotherapy-related LncRNAs. A back propagation (BP) network was then used to validate the predictive capacity of important LncRNAs. The molecular functions of hub LncRNAs were investigated via qRT-PCR and cell proliferation assay. Molecular-docking technique was used to explore candidate drug of targets of hub LncRNA in the model. Results: A total of 125 differentially expressed LncRNAs between sensitive and resistant patients. Seventeen important LncRNAs were identified via RF, and seven factors were identified via LR. With respect to SVM, the top 15 LncRNAs of AvgRank were selected. Five merge chemotherapy-related LncRNAs were used to predict chemotherapy resistance with high accuracy. CAHM was a hub LncRNA of model and expression high in sorafenib resistance cell lines. In addition, the results of CCK8 showed that the sensitivity of HepG2-sorafenib cells to sorafenib was significantly lower than that of HepG2; and the sensitivity of HepG2-sorafenib cells transfected with sh-CAHM was significantly higher than that of Sorafenib. In the non-transfection group, the results of clone formation experiments showed that the number of clones formed by HepG2-sorafenib cells treated with sorafenib was significantly more than that of HepG2; after HepG2-sorafenib cells were transfected with sh-CAHM, the number of clones formed by Sorafenib treatment was significantly higher than that of HepG2 cells. The number was significantly less than that of HepG2-s + sh-NC group. Molecular Docking results indicate that Moschus was candidate drug for target protein of CAHM. Conclusion: Five chemotherapy-related LncRNAs could predict drug resistance in HCC with high accuracy, and the hub LncRNA CAHM has potential as a new biomarker for HCC chemotherapy resistance.

Coarse-Grained Force Field for Polyethylene Oxide and Polyethylene Glycol Aqueous Solutions Based on a Polarizable Water Model.

A new, accurate and transferable coarse-grained (CG) force field (FF) for polyethylene oxide (PEO) and polyethylene glycol (PEG) aqueous solutions based on a polarizable CG water (PCGW) model is developed in this work. A PCGW bead, which represents four water molecules, is modeled as two charged dummy particles connected by two constrained bonds to a central neutral particle; a PEO or PEG oligomer is modeled as a chain with repeated middle beads (PEOM) representing diether groups and two terminal beads (PEOT or PEGT) of a different type compared to PEOM. To describe nonbonded van der Waals interactions, a piecewise Morse potential with four tunable parameters is used. The force parameters are automatically and rigorously optimized by a meta-multilinear interpolation parameterization (meta-MIP) algorithm to simultaneously match multiple thermodynamic properties, including the density, heat of vaporization, vapor-liquid interfacial tension, and solvation free energy of the pure PEO or PEG oligomer bulk system as well as the mixing density and hydration free energy of the oligomer/water binary mixture. Additional thermodynamic and structural properties for longer PEO and PEG polymer aqueous solutions, such as the self-diffusion coefficient, radius of gyration, and end-to-end distance, are predicted to test the accuracy and transferability of this new CG FF. Based on the PCGW model, the presented FF optimization algorithm and strategy can be extended to more complex polyelectrolytes and surfactants.

A top-down and bottom-up combined strategy for parameterization of coarse-grained force fields for phospholipids.

Coarse-graining (CG) molecular dynamics (MD) simulations are widely used in interpreting experimental observations and predicting assembly morphology as well as collective behaviour but also face the problem of poor accuracy. A main issue is that cross-termed interactions between different CG beads are inadequately parameterized. This work proposes a novel top-down and bottom-up combined strategy to parameterize both self- and cross-termed interactions of zwitterionic phospholipids in water solution based on a piecewise Morse potential describing nonbonded van der Waals interactions. The self-interacting force parameters were optimized by matching experimental density, heat vapourization, and surface tension in a top-down manner, while the cross-termed interactions were optimized by fitting pseudo properties obtained from atomistic simulations in a bottom-up way, including mixing density, intermolecular energy, and radial mixing coefficient. The transferability of the CG force field (FF) was confirmed by reproducing a variety of structural and thermodynamic properties of lipid membranes in both liquid and gel phases. This FF can well depict vesicle self-assembly and vesicle fusion processes. Matching pseudo properties opens a new way to develop CG FF with increased accuracy and transferability.

Thermodynamic Driving Forces for Divalent Cations Binding to Zwitterionic Phospholipid Membranes.

We calculated the free energies for calcium, magnesium, and zinc ions binding to a zwitterionic phospholipid bilayer by using molecular dynamics simulations and the enhanced umbrella sampling technique. By decomposing the free energy into entropic and enthalpic contributions, we found that Ca2+ has the highest binding affinity and that the overall process is endothermic combined with a secondary exothermic process at higher ion concentrations. The relatively low dehydration free energy of Ca2+ allows it to release coordinated water upon binding to the membrane. The dehydrated Ca2+ further coordinates with lipids, resulting in a weaker influence on the water orientation and increased entropy. However, when sufficient Ca2+ ions are adsorbed, the concentrated cation layer induces a positive electrostatic field, which enhances the energy barrier for further ion binding and orients the adjacent water, resulting in decreased entropy. In contrast, binding of Mg2+ and Zn2+ is exothermic and less favored because they remain fully hydrated when interacting with lipids.

Hydrophobicity Determines the Bacterial Killing Rate of α-Helical Antimicrobial Peptides and Influences the Bacterial Resistance Development.

Rapid antimicrobial action is an important advantage of antimicrobial peptides (AMPs) over antibiotics, which is also a reason for AMPs being less likely to induce bacterial resistance. However, the structural parameters and underlying mechanisms affecting the bacterial killing rate of AMPs remain unknown. In this study, we performed a structure-activity relationship (SAR) study using As-CATH4 and 5 as templates. We revealed that hydrophobicity, rather than other characteristics, is the critical structural parameter determining the bacterial killing rate of α-helical AMPs. With the hydrophobicity increase, the action rates of AMPs including bacterial binding, lipopolysaccharides neutralization, and outer and inner membrane permeabilization increased. Additionally, the higher hydrophobic AMPs with enhanced bacterial killing rates possess better in vivo therapeutic potency and a lower propensity to induce bacterial resistance. These findings revealed the importance of the bacterial killing rate for AMPs and are of great significance to the design and optimization of AMP-related drugs.

Polymyxins induce lipid scrambling and disrupt the homeostasis of Gram-negative bacteria membrane.

Polymyxins are increasingly used as the last-line therapeutic option for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. However, efforts to address the resistance in superbugs are compromised by a poor understanding of the bactericidal modes because high-resolution detection of the cell structure is still lacking. By performing molecular dynamics simulations at a coarse-grained level, here we show that polymyxin B (PmB) disrupts Gram-negative bacterial membranes by altering lipid homeostasis and asymmetry. We found that the binding of PmBs onto the asymmetric outer membrane (OM) loosens the packing of lipopolysaccharides (LPS) and induces unbalanced bending torque between the inner and outer leaflets, which in turn triggers phospholipids to flip from the inner leaflet to the outer leaflet to compensate for the stress deformation. Meanwhile, some LPSs may be detained on the inner membrane (IM). Then, the lipid-scrambled OM undergoes phase separation. Defects are created at the boundaries between LPS-rich domains and phospholipid-rich domains, which consequently facilitate the uptake of PmB across the OM. Finally, PmBs target LPSs detained on the IM and similarly perturb the IM. This lipid Scramble, membrane phase Separation, and peptide Translocation model depicts a novel mechanism by which polymyxins kill bacteria and sheds light on developing a new generation of polymyxins or antibiotic adjuvants with improved killing activities and higher therapeutic indices.

Structure and Formation Mechanism of Antimicrobial Peptides Temporin B- and L-Induced Tubular Membrane Protrusion.

Temporins are a family of antimicrobial peptides (AMPs) isolated from frog skin, which are very short, weakly charged, and highly hydrophobic. They execute bactericidal activities in different ways from many other AMPs. This work investigated morphological changes of planar bilayer membranes composed of mixed zwitterionic and anionic phospholipids induced by temporin B and L (TB and TL) using all-atom and coarse-grained molecular dynamics simulations. We found that TB and TL fold to α-helices at the membrane surface and penetrate shallowly into the bilayer. These short AMPs have low propensity to induce membrane pore formation but possess high ability to extract lipids out. At relatively high peptide concentrations, the strong hydrophobicity of TB and TL promotes them to aggregate into clusters on the membrane surface. These aggregates attract a large amount of lipids out of the membrane to release compression induced by other dispersed peptides binding to the membrane. The extruded lipids mix evenly with the peptides in the cluster and form tubule-like protrusions. Certain water molecules follow the movement of lipids, which not only fill the cavities of the protrusion but also assist in maintaining the tubular structures. In contrast, the peptide-free leaflet remains intact. The present results unravel distinctive antimicrobial mechanisms of temporins disturbing membranes.

A novel anionic cathelicidin lacking direct antimicrobial activity but with potent anti-inflammatory and wound healing activities from the salamander Tylototriton kweichowensis.

Cathelicidin is a family of antimicrobial peptides (AMPs) existing in vertebrates, which play multiple functions in host responses against environmental stresses. All cathelicidins identified to date are cationic, no anionic member with net negative charges has been reported. In the present study, a novel anionic cathelicidin (TK-CATH) with a net charge of -3 was identified from the skin of the salamander, T. kweichowensis. Unlike most other cathelicidin members, it didn't exhibit direct antimicrobial activity. However, it demonstrated strong anti-inflammatory activity. It effectively inhibited the LPS-induced pro-inflammatory cytokine gene expression and protein production in amphibian leukocytes and mouse macrophages by inhibiting the LPS-activated mitogen-activated protein kinase (MAPK) signaling pathways. Besides, TK-CATH showed potent wound healing activity. It could effectively induce the production of several cytokines, chemokines and growth factors relating to wound healing, promote the motility and proliferation of keratinocytes, and accelerate the skin wound healing in a mouse full-thickness wound model. These results imply that TK-CATH participates in both the inflammatory phase and new tissue formation phase of wound repair process. Meanwhile, TK-CATH exhibited weak but effective free radical scavenging activity and low cytotoxicity. All the results above indicate that TK-CATH is a multifunctional peptide in the skin of the salamander T. kweichowensis. It may play important roles in host immune responses against bacterial infection and skin wound repair.

Sorafenib prevents the proliferation and induces the apoptosis of liver cancer cells by regulating autophagy and hypoxia-inducible factor-1.

Sorafenib has been approved as a systemic drug for advanced liver cancer; however, the underlying mechanisms remain unclear. The present study aimed to investigate the effects of sorafenib on the proliferation, autophagy and apoptosis of HepG2 cells under hypoxia. Briefly, reverse transcription-quantitative PCR and western blotting was performed to quantify HIF-1, LC3II/I, mTOR and p70s6K expression levels. Cell proliferation was determined using the Cell Counting Kit-8 assay and the cell apoptosis rate was evaluated using flow cytometry. The results demonstrated that autophagy and apoptosis were induced by hypoxia, and that sorafenib further enhanced hypoxia-induced autophagy and apoptosis in HepG2 cells in a dose-dependent manner. Furthermore, the mechanism of sorafenib-mediated autophagy in liver cancer cell were investigated by using chloroquine (CQ). The results showed that CQ significantly inhibited autophagy by decreasing LC3II/LC3I ratio in HepG2 cells treated with sorafenib and/or hypoxia. By contrast, sorafenib could increase the expression of hypoxia-inducible factor-1 (HIF-1) and of the autophagy marker (LC3II/I) and decrease the expression of mammalian target of rapamycin and p70 ribosomal S6 kinase in HepG2 cells under normoxia and hypoxia conditions, suggesting that sorafenib could induce hypoxia and autophagy in liver cancer cells. In addition, sorafenib was demonstrated to prevent proliferation and induce apoptosis of HepG2 cells under normoxia and hypoxia. Sorafenib could also prevent the malignant behavior of HepG2 by inducing hypoxia and autophagy. In summary, the findings from the present study suggested that sorafenib may inhibit liver cancer progression by activating autophagy and HIF-1 signaling pathway.

Development of accurate coarse-grained force fields for weakly polar groups by an indirect parameterization strategy.

Coarse-grained (CG) molecular dynamics simulations are widely used to predict morphological structures and interpret mechanisms of mesoscopic behavior between the scope of traditional experiments and all-atom simulations. However, most current CG force fields (FFs) are not precise enough, especially for polar molecules or functional groups. A main obstacle in developing accurate CG FFs for polar molecules is the freezing problem met at room temperature. In this work, we introduce an indirect parametrization strategy for weakly polar groups by considering their short-chain homologs to avoid freezing. Here, a polar group containing three to four heavy atoms is mapped into one CG bead that is connected to one alkyl bead composed of three or four carbons. The CG beads interact via 4-parameter nonbonded Morse potentials and harmonic bonded potentials. An efficient meta-multilinear interpolation parameterization algorithm, as recently developed by us, is used to rigorously optimize the force parameters. Satisfactory accuracy is witnessed in terms of the density, heat of vaporization, surface tension, and solvation free energy of the homologs of twelve polar molecules, all deviating from the experiment by less than 5%. The transferability of the current FF is indicated by the predicted density, heat of vaporization, and end-to-end distance distributions of fatty acid methyl esters composed of multiple functional groups parameterized in this work.

Development of coarse-grained force field for alcohols: an efficient meta-multilinear interpolation parameterization algorithm.

Coarse-grained (CG) molecular dynamics are powerful tools to access a mesoscopic phenomenon and simultaneously record microscopic details, but currently the CG force fields (FFs) are still limited by low parameterization efficiency and poor accuracy especially for polar molecules. In this work, we developed a Meta-Multilinear Interpolation Parameterization (Meta-MIP) algorithm to optimize the CG FFs for alcohols. This algorithm significantly boosts parameterization efficiency by constructing on-the-fly local databases to cover the global optimal parameterization path. In specific, an alcohol molecule is mapped to a heterologous model composed of an OH bead and a hydrocarbon portion which consists of alkane beads representing two to four carbon atoms. Non-bonded potentials are described by soft Morse functions that have no tail-corrections but can still retain good continuities at truncation distance. Nearly all of the properties in terms of density, heat of vaporization, surface tension, and solvation free energy for alcohols predicted by the current FFs deviate from experimental values by less than 7%. This Meta-MIP algorithm can be readily applied to force field development for a wide variety of molecules or functional groups, in many situations including but not limited to CG FFs.

Soluble CD83 inhibits acute rejection by up regulating TGF-ß and IDO secretion in rat liver transplantation.

BACKGROUND: Allogeneic transplantation immune tolerance is currently a hot research issue and soluble CD83(sCD83) is a novel immunomodulator with great potential in inducing transplantation tolerance. OBJECTIVE: To investigate the mechanism of the immune tolerance effect of sCD83 on rat liver transplantation. METHOD: A rat liver transplantation model was established to study the effects of sCD83 on the expression levels of IL-2, IL-10, and TGF-ß in peripheral blood and the mRNA expressions of foxp3, TGF-ß, and Indoleamine 2,3-dioxygenase (IDO) in liver. The expression changes of costimulatory molecules CD80, CD86, and MHC-II on the surface of DC cells and the expressions of IDO + DC cell, TGF-ß + CD4 + T cell, and CD4 + CD25 + Foxp3 + T cell were analyzed and compared. RESULTS: sCD83 alleviated the rejection activity index (RAI) of rat liver transplantation in the early stage, increased the expressions of TGF-ß, IL-10 in peripheral blood and the mRNAs of IDO, TGF-ß and foxp3 in the transplanted liver, and down-regulated the expressions of MHC-II, CD86, and CD80 in DC cells, resulting in significant increased numbers of tolerogenic TGF-ß + CD4 + T cells, Treg cells, and IDO + DC cells with low expression. CONCLUSION: sCD83 inhibited acute rejection after liver transplantation in an allogeneic rat, and the mechanism was associated with the effect that sCD83 increased the expression of TGF-ß, activated IDO immunosuppressive pathway, and increased tolerogenic DC cells and Treg cells.

Polymyxin B Loosens Lipopolysaccharide Bilayer but Stiffens Phospholipid Bilayer.

Multidrug-resistant Gram-negative bacteria have increased the prevalence of a variety of serious diseases in modern times. Polymyxins are used as the last-line therapeutic options for the treatment of infections. However, the mechanism of action of polymyxins remains in dispute. In this work, we used a coarse-grained molecular dynamics simulation to investigate the mechanism of the cationic antimicrobial peptide polymyxin B (PmB) interacting with both the inner and outer membrane models of bacteria. Our results show that the binding of PmB disturbs the outer membrane by displacing the counterions, decreasing the orientation order of the lipopolysaccharide tail, and creating more lipopolysaccharide packing defects. Upon binding onto the inner membrane, in contrast to the traditional killing mechanism that antimicrobial peptides usually use to induce holes in the membrane, PmBs do not permeabilize the inner membrane but stiffen it by filling up the lipid packing defect, increasing the lipid tail order and the membrane bending rigidity as well as restricting the lipid diffusion. PmBs also mediate intermembrane contact and adhesion. These joint effects suggest that PmBs deprive the biological activity of Gram-negative bacteria by sterilizing the cell.

Development of Coarse-Grained Force Field by Combining Multilinear Interpolation Technique and Simplex Algorithm.

A fast, reasonable, and transferable coarse-grained (CG) molecular dynamics force field (FF) is essential to combine experimental and simulation data. However, the parameterization of CG FF usually requires massive computation, which hinders its rapid development. Here, we presented an efficient optimization protocol by combining multilinear interpolation technique with simplex algorithm. In this preliminary work, taking the experimental properties as the benchmark, we constructed a new set of CG FF for water and n-alkanes by adopting piecewise Morse function to describe the nonbonded interactions. This CG FF has a delicate balance between efficiency, accuracy, and transferability and well reproduced the correct structural and thermodynamics properties of pure water and alkane liquids. More importantly, optimized Morse potential was also successfully applied to describe the interactions between water and n-alkanes. It nicely predicted the phase separation, interface tension, hydration free energy, and formation of microemulsions of water/oil mixtures. © 2019 Wiley Periodicals, Inc.

Peripheral Antimicrobial Peptide Gomesin Induces Membrane Protrusion, Folding, and Laceration.

Optical microscopy shows that the peripheral antimicrobial peptide (AMP) gomesin does not disrupt the bacterial membrane by forming stable transmembrane pores but induces lipid accumulation domains, which is followed by a sudden burst near the domains. The molecular action mechanisms of gomesin on vesicle and planar bilayer membranes are investigated in this work using coarse-grained molecular dynamics simulations. By comparing the membrane morphology and property changes induced by gomesin and the pore-forming AMP melittin, we determined that the amphiphilic shape of the AMPs is a key factor affecting the mechanism of cell death. The binding of wedge-shaped gomesin, with a small hydrophobic surface, onto the membrane induces protrusion and folding of the outer monolayer followed by sudden membrane lacerations at the axillae of the protuberances. Alternatively, cylinder-shaped melittins with comparable hydrophilic and hydrophobic surfaces destroy membranes by forming stable pores coexisting with exocytosis-like buddings and endocytosis-like invaginations. The multiple actions of AMPs on the bacterial membrane suggest diverse paradigms for designing molecular carriers for delivering drugs to the cell.

Peptide-Lipid Interaction Sites Affect Vesicles' Responses to Antimicrobial Peptides.

This article presents coarse-grained molecular dynamics simulations of pore-forming antimicrobial peptide melittin and its interactions with vesicles composed of a mixture of zwitterionic and anionic phospholipids. Besides creating holes in the membrane, the adsorption of melittin also induces vesicle budding, which can develop into vesiculation at high peptide concentrations, as well as vesicle invagination, which can eventually result in a corrugated membrane surface. These rich morphology changes are mediated by the curvature of the vesicles and the peptide concentration. Highly curved vesicles favor the recruitment of melittins with a higher density of binding sites. The peptides mainly penetrate into the membrane surface in monomers via hydrophobic interaction. Lowly curved vesicles recruit melittins with a low density of binding sites. Surplus peptides are prone to form oligomers and shallowly adsorb on the surface of membrane via electrostatic interaction. The penetration of monomers induces membrane pore formation and positive membrane curvature, which promote vesicle budding. The adsorption of oligomers induces negative membrane curvature, which promotes vesicle invagination. This work demonstrates that antimicrobial peptides adopt multiple actions to destroy bacterial membranes.

Implicit-solvent dissipative particle dynamics force field based on a four-to-one coarse-grained mapping scheme.

A new set of efficient solvent-free dissipative particle dynamics (DPD) force fields was developed for phospholipids and peptides. To enhance transferability, this model maps around four heavy atoms and their connected hydrogen atoms into a coarse-grained elementary bead based on functional group. The effective hybrid potential between any pair of beads is composed of a short-range repulsive soft-core potential that directly adopts the form of an explicit-solvent DPD model and a long-range attractive hydrophobic potential. The parameters of the attractive potentials for lipid molecules were obtained by fitting the explicit-solvent DPD simulation of one bead of any type in a water box, then finely tuning it until the bilayer membrane properties obtained in the explicit-solvent model were matched. These parameters were further extended to amino acids according to bead type. The structural and elastic properties of bilayer membranes, free energy profiles for a lipid flip-flop and amino acid analogues translocating across the membrane, and membrane pore formation induced by antimicrobial peptides obtained from this solvent-free DPD force field considerably agreed with the explicit-solvent DPD results. Importantly, the efficiency of this method is guaranteed to accelerate the assembly of vesicles composed of several thousand lipids by up to 50-fold, rendering the experimental liposome dynamics as well as membrane-peptide interactions feasible at accessible computational expense.