Download or read book An Investigation of Protein and Antimicrobial Peptide Interactions with Model Lipid Membranes written by Mitaben D. Lad and published by . This book was released on 2006 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Peptide Lipid Interactions written by Sidney A. Simon and published by Academic Press. This book was released on 2002-11-13 with total page 606 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume contains a comprehensive overview of peptide-lipid interactions by leading researchers. The first part covers theoretical concepts, experimental considerations, and thermodynamics. The second part presents new results obtained through site-directed EPR, electron microscopy, NMR, isothermal calorimetry, and fluorescence quenching. The final part covers problems of biological interest, including signal transduction, membrane transport, fusion, and adhesion. Key Features * world-renowned experts * state-of-the-art experimental methods * monolayers, bilayers, biological membranes * theoretical aspects and computer simulations * rafts * synaptic transmission * membrane fusion * signal transduction
Download or read book Peptide and Protein Interaction with Membrane Systems written by Sara Bobone and published by Springer. This book was released on 2014-05-31 with total page 147 pages. Available in PDF, EPUB and Kindle. Book excerpt: In her thesis, Sara Bobone outlines spectroscopic studies of antimicrobial peptides (AMPs) which are promising lead compounds for drugs used to fight multidrug resistant bacteria. Bobone shows that AMPs interact with liposomes and she clarifies the structure of pores formed by one of these molecules. These results help us to understand how AMPs are selective for bacterial membranes and how their activity can be finely tuned by modifying their sequence. Findings which solve several conundrums debated in the literature for years. In addition, Bobone uses liposomes as nanotemplates for the photopolymerization of hydrogels - exploiting the self- assembly properties of phospholipids. Bobone was able to trap an enzyme using nanometeric particles, while still allowing its activity by the diffusion of substrates and products through the network of the polymer. The innovative nano devices described in this thesis could solve many of the hurdles still hampering the therapeutic application of protein-based drugs.
Download or read book Protein Lipid Interactions written by Lukas K. Tamm and published by John Wiley & Sons. This book was released on 2006-05-12 with total page 470 pages. Available in PDF, EPUB and Kindle. Book excerpt: In 17 contributions by leading research groups, this first comprehensive handbook in the field covers the interactions between proteins and lipids that make the fabric of biological membranes from every angle. It examines the relevant hermodynamic and structural issues from a basic science perspective, and goes on to discuss biochemical and cell biological processes. The book covers physical principles as well as mechanisms of membrane fusion and fission. Additionally, chapters on bilayer structure and protein-lipid interactions as well as on how proteins shape lipids and vice versa, membrane penetration by toxins, protein sorting, and allosteric regulation of signal transduction across membranes make this a valuable information source for researchers in academia and industry.
Download or read book Drug biomembrane interaction studies written by T. Musumeci and published by Elsevier Inc. Chapters. This book was released on 2013-10-31 with total page 24 pages. Available in PDF, EPUB and Kindle. Book excerpt: Antimicrobial agents are from different classes of molecules that suppress multiplication and growth of or kill microorganisms such as bacteria, fungi, or viruses. The precise mechanism of action of some antimicrobial agents is unknown but they must interact with or cross the cell membrane to have an effect. Identification of the damage induced by these compounds is difficult due to the complexity of cell membranes. Studying interactions using membrane models is a first step in obtaining elementary information about the effects of such drugs. We discuss interaction studies in the recent literature that use calorimetric techniques, regarding the mechanism of action or side effects of antimicrobial agents. For interaction studies with mimetic membrane models using DSC analysis, we will try to answer some key questions: (a) Does lipid composition affect the interaction? (b) Does the composition of bilayers influence the secondary structure of a peptide antimicrobial? (c) Does lipid polymorphism influence the activity and toxicity of the molecules? We underline the importance of phospholipids (neutral or anionic) chosen to produce biomembrane vesicles as models for the different studies.
Download or read book Interaction of Antimicrobial Peptides with Model Lipid Membranes written by Ahmad Arouri and published by . This book was released on 2009 with total page 178 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Insect Immunity written by Dan Hultmark and published by . This book was released on 1982 with total page 98 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Biomembranes written by Robert B. Gennis and published by Springer Science & Business Media. This book was released on 2013-04-17 with total page 549 pages. Available in PDF, EPUB and Kindle. Book excerpt: New textbooks at all levels of chemistry appear with great regularity. Some fields like basic biochemistry, organic reaction mechanisms, and chemical thermody namics are well represented by many excellent texts, and new or revised editions are published sufficiently often to keep up with progress in research. However, some areas of chemistry, especially many of those taught at the graduate level, suffer from a real lack of up-to-date textbooks. The most serious needs occur in fields that are rapidly changing. Textbooks in these subjects usually have to be written by scientists actually involved in the research which is advancing the field. It is not often easy to persuade such individuals to set time aside to help spread the knowledge they have accumulated. Our goal, in this series, is to pinpoint areas of chemistry where recent progress has outpaced what is covered in any available textbooks, and then seek out and persuade experts in these fields to produce relatively concise but instructive introductions to their fields. These should serve the needs of one semester or one quarter graduate courses in chemistry and biochemistry. In some cases, the availability of texts in active research areas should help stimulate the creation of new courses.
Download or read book Membrane active Protein Interactions with Phospholipid Bilayers written by Mohammad Hassan Khatami and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Membrane-active proteins are a class of proteins that interact with lipid membranes in the body. I study two kinds of membrane-active proteins, antimicrobial peptides (AMPs) and lung surfactant (LS) proteins. In the first part of my PhD project I did computer simulation studies with two AMPs, Gaduscidin-1 and -2 (GAD-1 and GAD-2). These peptides are histidine rich and thus expected to exhibit pH-dependent activity. In this work I have performed molecular dynamics (MD) simulations with the peptides in both histidine-charged and histidine-neutral forms, along with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid molecules, employing GROMACS software and an OPLS-AA force field. My results show a high tendency for pairs of histidines to interact with pore regions in both histidine-charged and histidine-neutral simulations. This work is published in Biophysica et Biochimica Acta (BBA)-Biomembranes (2014). In the second part of my PhD research I performed computational simulations on lung surfactant protein B (SP-B) interacting with lipid bilayer. SP-B is a hydrophobic protein with 79 residues, from the saposin superfamily. Because of the extreme hydrophobicity of SP-B, the experimental structure of the protein is unknown. Thus, I combined the Mini-B (a fragment of SP-B) experimental structure and homology modelling based on proteins in saposin family to construct my initial model of SP-B. I run MD (using OPLS-AA and PACE force fields) and replica-exchange MD (using PACE force field) simulations with GROMACS software. I modelled SP-B in open and bent (V-shaped) structures, placed within or near a POPC lipid bilayer. My results demonstrate energetically feasible structures for SP-B, in which salt bridges Membrane-active proteins are a class of proteins that interact with lipid membranes in the body. I study two kinds of membrane-active proteins, antimicrobial peptides (AMPs) and lung surfactant (LS) proteins. In the first part of my PhD project I did computer simulation studies with two AMPs, Gaduscidin-1 and -2 (GAD-1 and GAD-2). These peptides are histidine rich and thus expected to exhibit pH-dependent activity. In this work I have performed molecular dynamics (MD) simulations with the peptides in both histidine-charged and histidine-neutral forms, along with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid molecules, employing GROMACS software and an OPLS-AA force field. My results show a high tendency for pairs of histidines to interact with pore regions in both histidine-charged and histidine-neutral simulations. This work is published in Biophysica et Biochimica Acta (BBA)-Biomembranes (2014). In the second part of my PhD research I performed computational simulations on lung surfactant protein B (SP-B) interacting with lipid bilayer. SP-B is a hydrophobic protein with 79 residues, from the saposin superfamily. Because of the extreme hydrophobicity of SP-B, the experimental structure of the protein is unknown. Thus, I combined the Mini-B (a fragment of SP-B) experimental structure and homology modelling based on proteins in saposin family to construct my initial model of SP-B. I run MD (using OPLS-AA and PACE force fields) and replica-exchange MD (using PACE force field) simulations with GROMACS software. I modelled SP-B in open and bent (V-shaped) structures, placed within or near a POPC lipid bilayer. My results demonstrate energetically feasible structures for SP-B, in which salt bridges Membrane-active proteins are a class of proteins that interact with lipid membranes in the body. I study two kinds of membrane-active proteins, antimicrobial peptides (AMPs) and lung surfactant (LS) proteins. In the first part of my PhD project I did computer simulation studies with two AMPs, Gaduscidin-1 and -2 (GAD-1 and GAD-2). These peptides are histidine rich and thus expected to exhibit pH-dependent activity. In this work I have performed molecular dynamics (MD) simulations with the peptides in both histidine-charged and histidine-neutral forms, along with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid molecules, employing GROMACS software and an OPLS-AA force field. My results show a high tendency for pairs of histidines to interact with pore regions in both histidine-charged and histidine-neutral simulations. This work is published in Biophysica et Biochimica Acta (BBA)-Biomembranes (2014). In the second part of my PhD research I performed computational simulations on lung surfactant protein B (SP-B) interacting with lipid bilayer. SP-B is a hydrophobic protein with 79 residues, from the saposin superfamily. Because of the extreme hydrophobicity of SP-B, the experimental structure of the protein is unknown. Thus, I combined the Mini-B (a fragment of SP-B) experimental structure and homology modelling based on proteins in saposin family to construct my initial model of SP-B. I run MD (using OPLS-AA and PACE force fields) and replica-exchange MD (using PACE force field) simulations with GROMACS software. I modelled SP-B in open and bent (V-shaped) structures, placed within or near a POPC lipid bilayer. My results demonstrate energetically feasible structures for SP-B, in which salt bridges play a significant role. My simulations provide hypotheses for how SP-B promotes the rearrangement of planar lipid bilayers. Part of this work has been accepted for publication in Biophysica et Biochimica Acta (BBA)-Biomembranes (2016). In the third part of my project I employed solid state nuclear magnetic resonance (NMR) using 2H, 31P and 15N experiments, to study SP-B interacting with mechanically oriented lipid bilayer. Here, I used full-length 15N-labelled SP-B, which was recombinantly expressed in our lab, to find the orientation of protein with respect to the bilayer. In this part of my thesis, the final goal was to compare the experimental 15N spectra with the spectra, predicted from the structures we got from computational simulations to help define the protein's structure. Since, I was not able to gain 15N NMR signals in my SP-B in lipid bilayer experiments, I did not fulfill the final goal of this part of my project. However, I was able to predict 15N NMR spectra of my computational SP-B structures. My NMR results indicate that more optimization needs to be done to modify our SP-B preparation protocol to 1) increase the yields of isotope-labelled protein and 2) increase the protein:lipid ratio when refolding into lipids. My simulated 15N spectra indicate that uniform 15N-labelling is unlikely to constrain SP-B's structure and topology very much and it will likely be necessary to use a more specifically labelled sample for these experiments.
Download or read book Lipid Bilayers written by J. Katsaras and published by Springer Science & Business Media. This book was released on 2013-06-29 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt: Provides the reader with an up to date insight of the current state of the art in the field of lipid bilayer research and the important insights derived for the understanding of the complex and varied behaviour of biological membranes and its function.
Download or read book Membrane active Peptides written by Miguel A. R. B. Castanho and published by Internat'l University Line. This book was released on 2010 with total page 675 pages. Available in PDF, EPUB and Kindle. Book excerpt:
- Author : Stefania Piantavigna
- Publisher :
- Release : 2014
- ISBN :
- Pages : 738 pages
The Action of Antimicrobial Peptides on Supported Lipid Bilayers Investigated by Biophysical Methods
Download or read book The Action of Antimicrobial Peptides on Supported Lipid Bilayers Investigated by Biophysical Methods written by Stefania Piantavigna and published by . This book was released on 2014 with total page 738 pages. Available in PDF, EPUB and Kindle. Book excerpt: The emergence of bacteria that have developed resistance towards "traditional" antibiotics is becoming a serious global health threat. Consequently, alternative approaches are needed to find new drugs that can act directly as antibiotics or to assist traditional drugs to improve efficacy. The emergence of antimicrobial peptides (AMPs) as a possible new class offers promise. AMPs represent a large and varied group of "natural antibiotics" present in virtually every organism. However, in order to develop new drugs derived from AMPs knowledge of the bioactivity of these is needed, such as concentration ranges and specific bacterial targets. Of great practical importance is to have a comprehensive understanding of the mechanism of action of AMPs, so that the risk of cross-reactivity and development of new bacterial resistance is minimised. All AMPs interact with the cell membrane, which is a complex and dynamic system, mostly containing phospholipids and proteins. Phospholipids are not simple "bricks" of the membrane, but they themselves are involved in various cellular processes. Therefore, biomimetic membranes, e.g. supported lipid bilayers (SLBs), represent a valid approach for investigating the interactions between lipids and AMPs. Creation of a supported membrane reduces the complexity of those studies to just one variable. Many variables influence the formation of SLBs and a protocol regarding the formation of SLBs assembled on gold-coated sensors is described in Paper 1. The membrane deposition and the peptide-membrane interactions were investigated using a Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) (Paper 2). Thus, the action of various peptides were investigated with zwitterionic membranes, which contained negatively charged lipid (bacterial membranes), or cholesterol (mammalian membranes).The action of the two most widely studied AMPs, melittin and magainin 2, on SLBs, has been examined using QCM-D in Chapter 3. These peptides formed "toroidal pores", which lead to membrane disruption. However, the action of these peptides has been found to be both concentration and composition dependent.Many AMPs are enriched in a particular amino acid residue. The influence of several of these peptide residues has been investigated using QCM-D in Chapters 4, 5 and 6. The action of proline-rich peptides apidaecins HbI and HbII, the variant Api88 and oncocin peptides on SLBs, are illustrated in Papers 3, 4 and 5, respectively. These peptides were found to insert into the membrane without any evidence of disruption. The influence of lipid composition on the activity of the arginine-rich peptide Tat has also been investigated with QCM together with scanning electrochemical microscopy (SECM) (Chapter 5). The cell-penetrating Tat peptide was shown to act as a lytic AMP in the presence of negatively charged membranes (Papers 6 and 7).The addition of tryptophan residues in the sequence of a short arginine-rich peptide, (RW)3, caused a dramatic switch from cell penetrating to lytic activity, while the inclusion of ruthenocene in the peptide RcCO-W(RW)2 did not affect the peptide activity (Chapter 6).Finally, in Chapter 7, Uperin 3.5, an amyloid-like AMP, demonstrated that the amyloid fibrils are not necessary for the membrane-disruption. However, the action of Uperin 3.5 towards zwitterionic membranes is switched to insertion if cholesterol is present in the membrane. Thus, QCM has been demonstrated to be an invaluable technique for characterising, in real time, the action of various peptides on SLBs of bacterial mimetic composition and mammalian. However, the combination of QCM with other techniques e.g. SECM, is always encouraged to reinforce this data and to gain a wide perspective of activity.
Download or read book Interactions of Antimicrobial Peptides AMPs with Model Membranes at Different PH Values written by Gagandeep K. Sandhu and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Antimicrobial peptides (AMPs) are important components of the innate immune systems of many different organisms. Their amphipathic and cationic characteristics promote interactions with the cell membrane. Gad peptides are rich in histidine, and thus have the potential to exhibit pH-dependent activity. The major focus of this study was to understand how Gad peptides interact with model lipid membranes and how these interactions depend on the peptides' overall charge and the composition of the model membranes. 2H NMR spectroscopy was used to study the effect of Gad peptides on lipid acyl chain order of model lipid bilayers at different pH values. 2H NMR results revealed that membrane disruption by Gad peptides was not pH-dependent. Zeta potential measurements were used to study the binding of Gad peptides to model lipid membranes. The binding studies showed that for both Gad-1 and Gad-2 at low pH, less peptide binds to the membrane and the peptide interacts with a larger number of lipid molecules. Experiments performed with model membranes containing cardiolipin (CL) in the presence of Gad-1 showed that the presence of CL allows the membrane to accommodate more Gad-1. In the presence of CL the peptide binds more strongly with the membrane and interacts with a larger number of lipids. Taken together, these results suggest that Gad peptides might disrupt membrane integrity by clustering anionic lipids. Clustering of anionic lipids away from zwitterionic lipids by cationic AMPs might be a contributing mechanism, which does not exclude other mechanisms, including the carpet mechanism and pore formation. The chemical shift values of 15N NMR spectroscopy can give an insight about the positioning of peptides in lipid bilayer surfaces. 15N NMR observations showed that Gad-1 aligned parallel to the membrane surface. The study of AMP-membrane interactions will help to identify criteria to recognize the important features of natural AMP sequences involved in the antimicrobial action and thus assist in the design of AMP-based antibiotics to help overcome the problem of antimicrobial resistance.
Download or read book Antimicrobial Peptides written by Katsumi Matsuzaki and published by Springer. This book was released on 2019-04-12 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents an overview of antimicrobial peptides (AMPs), their mechanisms of antimicrobial action, other activities, and various problems that must still be overcome regarding their clinical application. Divided into four major parts, the book begins with a general overview of AMPs (Part I), and subsequently discusses the various mechanisms of antimicrobial action and methods for researching them (Part 2). It then addresses a range of activities other than antimicrobial action, such as cell penetration, antisepsis, anticancer, and immunomodulatory activities (Part 3), and explores the prospects of clinical application from various standpoints such as the selective toxicity, design, and discovery of AMPs (Part 4). A huge number of AMPs have been discovered in plants, insects, and vertebrates including humans, and constitute host defense systems against invading pathogenic microorganisms. Consequently, many attempts have been made to utilize AMPs as antibiotics. AMPs could help to solve the urgent problem of drug-resistant bacteria, and are also promising with regard to sepsis and cancer therapy. Gathering a wealth of information, this book will be a bible for all those seeking to develop antibiotics, anti-sepsis, or anticancer agents based on AMPs.
Download or read book Advances in Planar Lipid Bilayers and Liposomes written by Ales Iglic and published by Academic Press. This book was released on 2012-09-04 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in Planar Lipid Bilayers and Liposomes volumes cover a broad range of topics, including main arrangements of the reconstituted system, namely planar lipid bilayers as well as spherical liposomes. The invited authors present the latest results of their own research groups in this exciting multidisciplinary field. Incorporates contributions from newcomers and established and experienced researchers Explores the planar lipid bilayer systems and spherical liposomes from both theoretical and experimental perspectives Serves as an indispensable source of information for new scientists
Download or read book Biophysical Modelling of Antimicrobial Peptide s Interactions with Phospholipid and Lipopolysaccharide Membranes written by Shokoofeh Nourbakhsh and published by . This book was released on 2019 with total page 163 pages. Available in PDF, EPUB and Kindle. Book excerpt: Antimicrobial peptides (AMPs) are naturally-occurring peptide antibiotics. The way they work has inspired a vigorous search for optimized peptide antibiotics for fighting resistant bacteria. Cationic AMPs cleverly utilize their electrostatic interactions with the bacterial membrane to selectively attack bacteria. Here, we first present a physical model of membrane selectivity of these peptides. For this, we use model membranes: phospholipid bilayers, possibly carrying a certain fraction of anionic lipids. The simultaneous presence of several competing effects (e.g., lipid demixing and peptide-peptide interactions), however, poses a serious challenge to theoretical analysis. We first examine critically various models of peptide-membrane interactions and map out one, which incorporates adequately these competing effects as well as the geometry of various regions in membranes, occupied by bound peptides, anionic lipids within the interaction range of each peptide, and those outside this range. This leads to a systematically-improved model for peptide selectivity. Using the model, we relate the peptide's intrinsic (cell-independent) selectivity to an apparent, cell-dependent one, and clarify the relative roles of peptide parameters and cell densities in determining their selectivity. A natural consequence of this relationship is that the selectivity is more sensitive to peptide parameters at low cell densities; as a result, the optimal peptide charge, at which the selectivity is maximized, increases with the cell density such that this notion becomes less meaningful at high cell densities. It also enables us to map out intrinsic selectivity from apparent (cell-dependent) one or biologically-relevant one from "conveniently-measured" selectivity. This effort will benefit our endeavour in optimizing the peptide parameters for their enhanced selectivity in a physiological environment. We extend our effort to examine peptide adsorption on the outer membrane (OM) of Gram-negative bacteria (e.g., Escherichia coli). In particular, we focus our effort on developing a model for the interaction between AMPs and the wild-type lipopolysaccharide (LPS) layer in a biologically relevant medium, containing monovalent and divalent salt ions like Mg2+. This requires a non-trivial generalization of an earlier coarse-grained model, in which the effects of oligosaccharide and O-antigen chains are ignored. In our model, these effects are captured by modelling the LPS layer as forming a polymer brush on top of its anionic phosphate groups. Using this model, we examine how the presence of oligosaccharide and O-antigen chains modifies the binding of antimicrobials to the LPS layer. Our results demonstrate that the presence of the saccharide brush reduces the number of hydrophobically- bound peptides to the polymer-grafted interface of LPS, compared to the deep-rough LPS layer that lacks the polymer brush. Our LPS brush model predicts [sim] 30% reduction of peptide adsorption, which is consistent with recent experimental measurements. This can be attributed to the steric hindrance of the brush or the excluded-volume interaction of the saccharide chains with peptides. At a low cell density limit, we also note that the total number of peptides trapped within the brush is very small, compared to the number of bound peptides on the LPS interface. This implies that the hydrophobic binding of peptides is insensitive to brush lengths. This, however, does not exclude the possibility of kinetic slowing-down of the binding.
Download or read book Molecular Dynamics Studies on Peptide Partitioning and Ion Translocation in Biological Membranes written by Peiran Chen and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Biological membranes, mainly composed of lipid bilayers and proteins, are important in all the cells. Proteins in the membrane carry out most of the membrane functions. Knowledge about the protein-lipid interactions is essential to understanding the function of both protein and lipid. Some of the proteins that are hydrophobic can effectively partition into membranes, however, for those with charged residues, there have been intense debates on the partitioning energetics and charged protein-lipid interactions. Traditional views of the hydrophobic membrane interior as a hostile environment for charged species have been challenged by recent membrane protein experiments. Furthermore, charged proteins play important roles in many protein functions, such as antimicrobial peptides, ion channels, and cell penetrating peptides. To resolve such controversies, this thesis focuses on charged protein-lipid interactions to study the peptide partitioning energetics and ion translocation mechanisms in membranes. All-atom Molecular Dynamics (MD) simulations have been applied in the simulations of poly-Alanine peptide with one arginine (Arg) sidechain partitioning into Dipalmitoylphosphatidylcholine (DPPC) membranes. This peptide, which is a simplified model from the GWALP peptide widely used in protein partitioning experiments, is both a good comparison to experiments and an easy model for method developing. This study generated new methods to improve free energy calculations in residue mutation and movements. With these methods, we demonstrated that the partitioning of a transmembrane helix containing one Arg sidechain involved a free energy penalty of ~ 20kcal/mol, which is affected by various factors such as peptide tilting, peptide rotation, and anchor strength. Furthermore, this study was a new attempt in simulating the partitioning of realistic peptides using all-atom models. From this study, we showed the advantages and difficulties of simulating real peptide, which provided direct connections between MD simulations and biological experiments. In the study of mechanisms of ion translocation in membranes, membrane thickness was suggested as an important factor in previous research, while membrane polarizability has not been well investigated in the past, thus we are especially interested in the role of membrane thickness and polarizability in this thesis. We predicted two mechanisms, including the ion-induced defect mechanism which involves membrane deformations and energy cost growing with membrane thickness, and the solubility diffusion mechanism involving ion partitioning, for which we predicted a cost of 25~30 kcal/mol according to the previous research. All-atom MD simulations of an Arg side chain analog, MguanH+, moving across bilayers of mono-unsaturated phosphatidylcholine (PC) lipids with and without cholesterol of a wide range of thicknesses have been performed, in order to study the effect of membrane thickness on the charged protein-lipid interactions. Moreover, to understand the role of polarizability on the ion translocation mechanism, both polarizable and non-polarizable models have been applied to PC bilayers of interest. For all non-polarizable membranes, the ion translocation caused membrane deformations, leading to sharp free energy barriers ranging from 14 kcal/mol to 40 kcal/mol with similar shapes and slopes, which indicated an ion-induced defect mechanism in non-polarizable models. However, in polarizable models, ion translocation was found to start with an ion-induced defect mechanism, and then transfer to a solubility-diffusion mechanism when the free energy cost reached 26 kcal/mol, from which an upper limit of ion translocation energy barrier of 26 kcal/mol has been demonstrated for the first time. Furthermore, membrane polarizability has been proved essential in sampling the changing membrane charge transport mechanisms. With MD simulations we were able to achieve deeper understanding of the charge-lipid interactions and mechanisms governing peptide partitioning and ion translocation at the atomic level. This research will help understand a broad range of biological phenomena involving protein partitioning and translocations, such as the mechanisms of viral peptides and cell penetrating peptides, the invention of new functionalized bionanodevices or drug delivery, voltage gated ion channel function to treat various disorders, and for basic knowledge of proteins that control our nervous systems.