The Experts below are selected from a list of 2322 Experts worldwide ranked by ideXlab platform
Annelise E. Barron - One of the best experts on this subject based on the ideXlab platform.
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Halogenation as a tool to tune antimicrobial activity of Peptoids
Scientific Reports, 2020Co-Authors: Natalia Molchanova, Annelise E. Barron, Josefine Eilsø Nielsen, Kristian B. Sørensen, Bala Krishna Prabhala, Paul Robert Hansen, Reidar Lund, Håvard JenssenAbstract:Antimicrobial peptides have attracted considerable interest as potential new class of antibiotics against multi-drug resistant bacteria. However, their therapeutic potential is limited, in part due to susceptibility towards enzymatic degradation and low bioavailability. Peptoids (oligomers of N -substituted glycines) demonstrate proteolytic stability and better bioavailability than corresponding peptides while in many cases retaining antibacterial activity. In this study, we synthesized a library of 36 Peptoids containing fluorine, chlorine, bromine and iodine atoms, which vary by length and level of halogen substitution in position 4 of the phenyl rings. As we observed a clear correlation between halogenation of an inactive model Peptoid and its increased antimicrobial activity, we designed chlorinated and brominated analogues of a known Peptoid and its shorter counterpart. Short brominated analogues displayed up to 32-fold increase of the activity against S. aureus and 16- to 64-fold against E. coli and P. aeruginosa alongside reduced cytotoxicity. The biological effect of halogens seems to be linked to the relative hydrophobicity and self-assembly properties of the compounds. By small angle X-ray scattering (SAXS) we have demontrated how the self-assembled structures are dependent on the size of the halogen, degree of substitution and length of the Peptoid, and correlated these features to their activity.
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prostate tumor specific peptide Peptoid hybrid prodrugs
Bioorganic & Medicinal Chemistry Letters, 2015Co-Authors: Jiyoun Lee, Annelise E. Barron, Wei Huang, James M Broering, Jiwon SeoAbstract:Abstract Inspired by naturally occurring host defense peptides, cationic amphipathic Peptoids provide a promising scaffold for anti-cancer therapeutics. Herein, we report a library of peptide–Peptoid hybrid prodrugs that can be selectively activated by prostate cancer cells. We have identified several compounds demonstrating potent anti-cancer activity with good to moderate selectivity. We believe that these prodrugs can provide a useful design principle for next generation peptide–Peptoid hybrid prodrugs.
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short alkylated Peptoid mimics of antimicrobial lipopeptides
Antimicrobial Agents and Chemotherapy, 2011Co-Authors: Nathaniel P Chongsiriwatana, Modi Wetzler, Tyler M Miller, Sergei Vakulenko, Amy J Karlsson, Sean P Palecek, Shahriar Mobashery, Annelise E. BarronAbstract:We report the creation of alkylated poly-N-substituted glycine (Peptoid) mimics of antimicrobial lipopeptides with alkyl tails ranging from 5 to 13 carbons. In several cases, alkylation significantly improved the selectivity of the Peptoids with no loss in antimicrobial potency. Using this technique, we synthesized an antimicrobial Peptoid only 5 monomers in length with selective, broad-spectrum antimicrobial activity as potent as previously reported dodecameric Peptoids and the antimicrobial peptide pexiganan.
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novel Peptoid building blocks synthesis of functionalized aromatic helix inducing submonomers
Organic Letters, 2010Co-Authors: Jiwon Seo, Annelise E. Barron, Ronald N. ZuckermannAbstract:Peptoids, oligo-N-substituted glycines, can fold into well-defined helical secondary structures. The design and synthesis of new Peptoid building blocks that are capable of both (a) inducing a helical secondary structure and (b) decorating the helices with chemical functionalities are reported. Peptoid heptamers containing carboxamide, carboxylic acid or thiol functionalities were synthesized, and the resulting Peptoids were shown to form stable helices. A thiol-containing Peptoid readily formed the homodisulfide, providing a convenient route to prepare Peptoid helix homodimers.
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soft x ray tomography of phenotypic switching and the cellular response to antifungal Peptoids in candida albicans
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Maho Uchida, Annelise E. Barron, Gerry Mcdermott, Modi Wetzler, Mark Le A Gros, Markko Myllys, Christian Knoechel, Carolyn A LarabellAbstract:The opportunistic pathogen Candida albicans can undergo phenotypic switching between a benign, unicellular phenotype and an invasive, multicellular form that causes candidiasis. Increasingly, strains of Candida are becoming resistant to antifungal drugs, making the treatment of candidiasis difficult, especially in immunocompromised or critically ill patients. Consequently, there is a pressing need to develop new drugs that circumvent fungal drug-resistance mechanisms. In this work we used soft X-ray tomography to image the subcellular changes that occur as a consequence of both phenotypic switching and of treating C. albicans with antifungal Peptoids, a class of candidate therapeutics unaffected by drug resistance mechanisms. Peptoid treatment suppressed formation of the pathogenic hyphal phenotype and resulted in striking changes in cell and organelle morphology, most dramatically in the nucleus and nucleolus, and in the number, size, and location of lipidic bodies. In particular, Peptoid treatment was seen to cause the inclusion of lipidic bodies into the nucleus.
Ronald N. Zuckermann - One of the best experts on this subject based on the ideXlab platform.
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dna origami protection and molecular interfacing through engineered sequence defined Peptoids
Proceedings of the National Academy of Sciences of the United States of America, 2020Co-Authors: Shihting Wang, Ronald N. Zuckermann, Melissa A Gray, Sunting Xuan, James Byrnes, Andy I Nguyen, Nevena Todorova, Molly M Stevens, Carolyn R Bertozzi, Oleg GangAbstract:DNA nanotechnology has established approaches for designing programmable and precisely controlled nanoscale architectures through specific Watson−Crick base-pairing, molecular plasticity, and intermolecular connectivity. In particular, superior control over DNA origami structures could be beneficial for biomedical applications, including biosensing, in vivo imaging, and drug and gene delivery. However, protecting DNA origami structures in complex biological fluids while preserving their structural characteristics remains a major challenge for enabling these applications. Here, we developed a class of structurally well-defined Peptoids to protect DNA origamis in ionic and bioactive conditions and systematically explored the effects of Peptoid architecture and sequence dependency on DNA origami stability. The applicability of this approach for drug delivery, bioimaging, and cell targeting was also demonstrated. A series of Peptoids (PE1–9) with two types of architectures, termed as “brush” and “block,” were built from positively charged monomers and neutral oligo-ethyleneoxy monomers, where certain designs were found to greatly enhance the stability of DNA origami. Through experimental and molecular dynamics studies, we demonstrated the role of sequence-dependent electrostatic interactions of Peptoids with the DNA backbone. We showed that octahedral DNA origamis coated with Peptoid (PE2) can be used as carriers for anticancer drug and protein, where the Peptoid modulated the rate of drug release and prolonged protein stability against proteolytic hydrolysis. Finally, we synthesized two alkyne-modified Peptoids (PE8 and PE9), conjugated with fluorophore and antibody, to make stable DNA origamis with imaging and cell-targeting capabilities. Our results demonstrate an approach toward functional and physiologically stable DNA origami for biomedical applications.
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unconstrained Peptoid tetramer exhibits a predominant conformation in aqueous solution
Biopolymers, 2019Co-Authors: Leah T Roe, Stephen Whitelam, Jeffrey G Pelton, John R Edison, Glenn L Butterfoss, Blakely W Tresca, Bridgette A Lafaye, David E Wemmer, Ronald N. ZuckermannAbstract:Conformational control in Peptoids, N-substituted glycines, is crucial for the design and synthesis of biologically-active compounds and atomically-defined nanomaterials. While there are a growing number of structural studies in solution, most have been performed with conformationally-constrained short sequences (e.g., sterically-hindered sidechains or macrocyclization). Thus, the inherent degree of heterogeneity of unconstrained Peptoids in solution remains largely unstudied. Here, we explored the folding landscape of a series of simple Peptoid tetramers in aqueous solution by NMR spectroscopy. By incorporating specific 13 C-probes into the backbone using bromoacetic acid-2-13 C as a submonomer, we developed a new technique for sequential backbone assignment of Peptoids based on the 1,n-Adequate pulse sequence. Unexpectedly, two of the tetramers, containing an N-(2-aminoethyl)glycine residue (Nae), had preferred conformations. NMR and molecular dynamics studies on one of the tetramers showed that the preferred conformer (52%) had a trans-cis-trans configuration about the three amide bonds. Moreover, >80% of the ensemble contained a cis amide bond at the central amide. The backbone dihedral angles observed fall directly within the expected minima in the Peptoid Ramachandran plot. Analysis of this compound against similar Peptoid analogs suggests that the commonly used Nae monomer plays a key role in the stabilization of Peptoid structure via a side-chain-to-main-chain interaction. This discovery may offer a simple, synthetically high-yielding approach to control Peptoid structure, and suggests that Peptoids have strong intrinsic conformational preferences in solution. These findings should facilitate the predictive design of folded Peptoid structures, and accelerate application in areas ranging from drug discovery to biomimetic nanoscience.
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universal relationship between molecular structure and crystal structure in Peptoid polymers and prevalence of the cis backbone conformation
Journal of the American Chemical Society, 2018Co-Authors: Douglas R Greer, Michael A Stolberg, Joyjit Kundu, Ryan K Spencer, Tod A Pascal, David Prendergast, Nitash P Balsara, Ronald N. ZuckermannAbstract:Peptoid polymers are often crystalline in the solid-state as examined by X-ray scattering, but thus far, there has been no attempt to identify a common structural motif among them. In order to probe the relationship between molecular structure and crystal structure, we synthesized and analyzed a series of crystalline Peptoid copolymers, systematically varying Peptoid side-chain length (S) and main-chain length (N). We also examined X-ray scattering data from 18 previously reported Peptoid polymers. In all Peptoids, we found that the unit cell dimensions, a, b, and c, are simple functions of S and N: a (A) = 4.55, b (A) = [2.98]N + 0.35, and c (A) = [1.86]S + 5.5. These relationships, which apply to both bulk crystals and self-assembled nanosheets in water, indicate that the molecules adopt extended, planar conformations. Furthermore, we performed molecular dynamics simulations (MD) of Peptoid polymer lattices, which indicate that all backbone amides adopt the cis conformation. This is a surprising conclusion, because previous studies on isolated molecules indicated an energetic preference for the trans conformer. This study demonstrates that when packed into supramolecular lattices or crystals, Peptoid polymers prefer to adopt a regular, extended, all-cis secondary structure.
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Universal Relationship between Molecular Structure and Crystal Structure in Peptoid Polymers and Prevalence of the cis Backbone Conformation
2018Co-Authors: Douglas R. Greer, Michael A Stolberg, Joyjit Kundu, Ryan K Spencer, David Prendergast, Nitash P Balsara, Tod Pascal, Ronald N. ZuckermannAbstract:Peptoid polymers are often crystalline in the solid-state as examined by X-ray scattering, but thus far, there has been no attempt to identify a common structural motif among them. In order to probe the relationship between molecular structure and crystal structure, we synthesized and analyzed a series of crystalline Peptoid copolymers, systematically varying Peptoid side-chain length (S) and main-chain length (N). We also examined X-ray scattering data from 18 previously reported Peptoid polymers. In all Peptoids, we found that the unit cell dimensions, a, b, and c, are simple functions of S and N: a (Å) = 4.55, b (Å) = [2.98]N + 0.35, and c (Å) = [1.86]S + 5.5. These relationships, which apply to both bulk crystals and self-assembled nanosheets in water, indicate that the molecules adopt extended, planar conformations. Furthermore, we performed molecular dynamics simulations (MD) of Peptoid polymer lattices, which indicate that all backbone amides adopt the cis conformation. This is a surprising conclusion, because previous studies on isolated molecules indicated an energetic preference for the trans conformer. This study demonstrates that when packed into supramolecular lattices or crystals, Peptoid polymers prefer to adopt a regular, extended, all-cis secondary structure
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exploring the links between Peptoid antibacterial activity and toxicity
MedChemComm, 2017Co-Authors: Hannah L Bolt, Ronald N. Zuckermann, Gabriela A Eggimann, Colin A B Jahoda, Gary J Sharples, Steven L CobbAbstract:Peptoids are a promising class of antimicrobial agents with reported activities against a range of both Gram-positive and Gram-negative bacteria, fungi and most recently parasites. However, at present the available toxicity data is somewhat limited and as such rationally designing effective antimicrobial Peptoids can be challenging. Herein, we present the toxicity profiling of a series of linear Peptoids against mammalian cell lines (HaCaT and HepG2). The cytotoxicity of the Peptoid library has then been correlated with their antibacterial properties against Gram-positive and Gram-negative bacteria and also to the hydrophobicity of the Peptoid sequences. The work presented provides valuable data to aid in the future rational design of antimicrobial Peptoids.
Kent Kirshenbaum - One of the best experts on this subject based on the ideXlab platform.
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hydrophobic interactions modulate antimicrobial Peptoid selectivity towards anionic lipid membranes
Biochimica et Biophysica Acta, 2018Co-Authors: Konstantin Andreev, Michael W Martynowycz, Mia L Huang, Ivan Kuzmenko, Kent Kirshenbaum, David GidalevitzAbstract:Abstract Hydrophobic interactions govern specificity for natural antimicrobial peptides. No such relationship has been established for synthetic Peptoids that mimic antimicrobial peptides. Peptoid macrocycles synthesized with five different aromatic groups are investigated by minimum inhibitory and hemolytic concentration assays, epifluorescence microscopy, atomic force microscopy, and X-ray reflectivity. Peptoid hydrophobicity is determined using high performance liquid chromatography. Disruption of bacterial but not eukaryotic lipid membranes is demonstrated on the solid supported lipid bilayers and Langmuir monolayers. X-ray reflectivity studies demonstrate that intercalation of Peptoids with zwitterionic or negatively charged lipid membranes is found to be regulated by hydrophobicity. Critical levels of Peptoid selectivity are demonstrated and found to be modulated by their hydrophobic groups. It is suggested that Peptoids may follow different optimization schemes as compared to their natural analogues.
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a rotamer library to enable modeling and design of Peptoid foldamers
Journal of the American Chemical Society, 2014Co-Authors: Douglas P Renfrew, Kent Kirshenbaum, Glenn L Butterfoss, Timothy W Craven, Richard BonneauAbstract:Peptoids are a family of synthetic oligomers composed of N-substituted glycine units. Along with other “foldamer” systems, Peptoid oligomer sequences can be predictably designed to form a variety of stable secondary structures. It is not yet evident if foldamer design can be extended to reliably create tertiary structure features that mimic more complex biomolecular folds and functions. Computational modeling and prediction of Peptoid conformations will likely play a critical role in enabling complex biomimetic designs. We introduce a computational approach to provide accurate conformational and energetic parameters for Peptoid side chains needed for successful modeling and design. We find that Peptoids can be described by a “rotamer” treatment, similar to that established for proteins, in which the Peptoid side chains display rotational isomerism to populate discrete regions of the conformational landscape. Because of the insufficient number of solved Peptoid structures, we have calculated the relative e...
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biomimetic Peptoid oligomers as dual action antifreeze agents
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Mia L Huang, Kent Kirshenbaum, David Ehre, Qi Jiang, Michael D WardAbstract:The ability of natural peptides and proteins to influence the formation of inorganic crystalline materials has prompted the design of synthetic compounds for the regulation of crystal growth, including the freezing of water and growth of ice crystals. Despite their versatility and ease of structural modification, peptidomimetic oligomers have not yet been explored extensively as crystallization modulators. This report describes a library of synthetic N-substituted glycine Peptoid oligomers that possess “dual-action” antifreeze activity as exemplified by ice crystal growth inhibition concomitant with melting temperature reduction. We investigated the structural features responsible for these phenomena and observed that Peptoid antifreeze activities depend both on oligomer backbone structure and side chain chemical composition. These studies reveal the capability of Peptoids to act as ice crystallization regulators, enabling the discovery of a unique and diverse family of synthetic oligomers with potential as antifreeze agents in food production and biomedicine.
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de novo structure prediction and experimental characterization of folded Peptoid oligomers
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Glenn L Butterfoss, Ken A. Dill, Ilya Chorny, Ronald N. Zuckermann, Kent Kirshenbaum, Richard Bonneau, Barney Yoo, Jonathan N Jaworski, Vincent A. VoelzAbstract:Peptoid molecules are biomimetic oligomers that can fold into unique three-dimensional structures. As part of an effort to advance computational design of folded oligomers, we present blind-structure predictions for three Peptoid sequences using a combination of Replica Exchange Molecular Dynamics (REMD) simulation and Quantum Mechanical refinement. We correctly predicted the structure of a N-aryl Peptoid trimer to within 0.2 A rmsd-backbone and a cyclic Peptoid nonamer to an accuracy of 1.0 A rmsd-backbone. X-ray crystallographic structures are presented for a linear N-alkyl Peptoid trimer and for the cyclic Peptoid nonamer. The Peptoid macrocycle structure features a combination of cis and trans backbone amides, significant nonplanarity of the amide bonds, and a unique "basket" arrangement of (S)-N(1-phenylethyl) side chains encompassing a bound ethanol molecule. REMD simulations of the Peptoid trimers reveal that well folded Peptoids can exhibit funnel-like conformational free energy landscapes similar to those for ordered polypeptides. These results indicate that physical modeling can successfully perform de novo structure prediction for small Peptoid molecules.
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a comparison of linear and cyclic Peptoid oligomers as potent antimicrobial agents
ChemMedChem, 2012Co-Authors: Mia L Huang, Sung Bin Y Shin, Meredith A Benson, Victor J Torres, Kent KirshenbaumAbstract:We investigated the antimicrobial activities of N-substituted glycine "Peptoid" oligomers incorporating cationic and hydrophobic side chains. Head-to-tail macrocyclization was employed to enhance antimicrobial activity. Both linear and cyclic Peptoids, ranging from six to ten residues, demonstrate potent antimicrobial activity against Gram-positive and Gram-negative bacteria. These Peptoids do not cause significant lysis of human erythrocytes, indicating selective antimicrobial activity. Conformational ordering established upon macrocyclization is generally associated with an enhanced capacity to inhibit bacterial cell growth. Moreover, increased hydrophobic surface area also plays a role in improving antimicrobial activity. We demonstrate the potency of a cyclic Peptoid in exerting antimicrobial activity against clinical strains of S. aureus while deterring the emergence of antimicrobial resistance.
Steven L Cobb - One of the best experts on this subject based on the ideXlab platform.
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Fluorinated Aromatic Monomers as Building Blocks To Control α‑Peptoid Conformation and Structure
2019Co-Authors: Diana Gimenez, Vincent A. Voelz, Guangfeng Zhou, Matthew F. D. Hurley, Juan A. Aguilar, Steven L CobbAbstract:Peptoids are peptidomimetics of interest in the fields of drug development and biomaterials. However, obtaining stable secondary structures is challenging, and designing these requires effective control of the Peptoid tertiary amide cis/trans equilibrium. Herein, we report new fluorine-containing aromatic monomers that can control Peptoid conformation. Specifically, we demonstrate that a fluoro-pyridine group can be used to circumvent the need for monomer chirality to control the cis/trans equilibrium. We also show that incorporation of a trifluoro-methyl group (NCF3Rpe) rather than a methyl group (NRpe) at the α-carbon of a monomer gives rise to a 5-fold increase in cis-isomer preference
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recent advances in the synthesis of Peptoid macrocycles
Chemistry: A European Journal, 2018Co-Authors: Alexandra M Webster, Steven L CobbAbstract:Over the past two decades, developing medical applications for peptides has, and continues to be a highly active area of research. At present there are over 60 peptide-based drugs on the market and more than 140 in various stages of clinical trials. The interest in peptide-based therapeutics arises from their biocompatibility and their ability to form defined secondary and tertiary structures, resulting in a high selectivity for complex targets. However, there are significant challenges associated with the development of peptide-based therapeutics, namely peptides are readily metabolised in vivo. Peptoids are an emerging class of peptidomimetic and they offer an alternative to peptides. Peptoids are comprised of N-substituted glycines where side-chains are located on the nitrogen atom of the amide backbone rather than the α-carbon as is the case in peptides. This change in structure confers a high degree of resistance to proteolytic degradation but the absence of any backbone hydrogen bonding means that Peptoids exhibit a high degree of conformational flexibility. Cyclisation has been explored as one possible route to rigidify Peptoid structures, making them more selective, and, therefore more desirable as potential therapeutics. This review outlines the various strategies that have been developed over the last decade to access new types of macrocyclic Peptoids.
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exploring the links between Peptoid antibacterial activity and toxicity
MedChemComm, 2017Co-Authors: Hannah L Bolt, Ronald N. Zuckermann, Gabriela A Eggimann, Colin A B Jahoda, Gary J Sharples, Steven L CobbAbstract:Peptoids are a promising class of antimicrobial agents with reported activities against a range of both Gram-positive and Gram-negative bacteria, fungi and most recently parasites. However, at present the available toxicity data is somewhat limited and as such rationally designing effective antimicrobial Peptoids can be challenging. Herein, we present the toxicity profiling of a series of linear Peptoids against mammalian cell lines (HaCaT and HepG2). The cytotoxicity of the Peptoid library has then been correlated with their antibacterial properties against Gram-positive and Gram-negative bacteria and also to the hydrophobicity of the Peptoid sequences. The work presented provides valuable data to aid in the future rational design of antimicrobial Peptoids.
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enlarging the chemical space of anti leishmanials a structure activity relationship study of Peptoids against leishmania mexicana a causative agent of cutaneous leishmaniasis
MedChemComm, 2016Co-Authors: Hannah L Bolt, Gabriela A Eggimann, Paul W Denny, Steven L CobbAbstract:Peptoids, a class of peptide mimetics, have emerged as promising anti-infective agents against a range of bacterial and fungal infections. Recently we have shown Peptoids to be novel anti-parasitic and, specifically, anti-leishmanial, compounds. In this study, we have expanded the chemical space of our Peptoid library and have identified Peptoids with low micromolar activity against Leishmania mexicana axenic amastigotes and significantly, the first Peptoids with promising activity against intracellular amastigotes, which are the clinical cause of cutaneous leishmaniasis.
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pep calc com a set of web utilities for the calculation of peptide and Peptoid properties and automatic mass spectral peak assignment
Journal of Computer-aided Molecular Design, 2016Co-Authors: Sam Lear, Steven L CobbAbstract:The ability to calculate molecular properties such as molecular weights, isoelectric points, and extinction coefficients is vital for scientists using and/or synthesizing peptides and Peptoids for research. A suite of two web utilities: Peptide Calculator and Peptoid Calculator, available free at http://www.pep-calc.com, are presented. Both tools allow the calculation of peptide/Peptoid chemical formulae and molecular weight, ChemDraw structure file export and automatic assignment of mass spectral peaks to deletion sequences and metal/protecting group adducts. Peptide Calculator also provides a calculated isoelectric point, molar extinction coefficient, graphical peptide charge summary and β-strand contiguity profile (for aggregation-prone sequences), indicating potential regions of synthesis difficulty. In addition to the unique automatic spectral assignment features offered across both utilities, Peptoid Calculator represents a first-of-a-kind resource for researchers in the field of Peptoid science. With a constantly expanding database of over 120 amino acids, non-natural peptide building blocks and Peptoid building blocks, it is anticipated that Pep-Calc.com will act as a valuable asset to those working on the synthesis and/or application of peptides and Peptoids in the biophysical and life sciences fields.
Jim Pfaendtner - One of the best experts on this subject based on the ideXlab platform.
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martini compatible coarse grained model for the mesoscale simulation of Peptoids
Journal of Physical Chemistry B, 2020Co-Authors: Mingfei Zhao, Chunlong Chen, Janani Sampath, Sarah Alamdari, Gillian Shen, Christopher J Mundy, Jim PfaendtnerAbstract:Peptoids (poly-N-substituted glycines) are a class of synthetic polymers that are regioisomers of peptides (poly-C-substituted glycines), in which the point of side-chain connectivity is shifted from the backbone C to the N atom. Peptoids have found diverse applications as peptidomimetic drugs, protein mimetic polymers, surfactants, and catalysts. Computational modeling is valuable in the understanding and design of Peptoid-based nanomaterials. In this work, we report the bottom-up parameterization of coarse-grained Peptoid force fields based on the MARTINI peptide force field against all-atom Peptoid simulation data. Our parameterization pipeline iteratively refits coarse-grained bonded interactions using iterative Boltzmann inversion and nonbonded interactions by matching the potential of mean force for chain extension. We assure good sampling of the amide bond cis/trans isomerizations in the all-atom simulation data using parallel bias metadynamics. We develop coarse-grained models for two representative Peptoids-polysarcosine (poly(N-methyl glycine)) and poly(N-((4-bromophenyl)ethyl)glycine)-and show their structural and thermodynamic properties to be in excellent accord with all-atom calculations but up to 25-fold more efficient and compatible with MARTINI force fields. This work establishes a new rigorously parameterized coarse-grained Peptoid force field for the understanding and design of Peptoid nanomaterials at length and time scales inaccessible to all-atom calculations.
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Peptoid backbone flexibilility dictates its interaction with water and surfaces a molecular dynamics investigation
Biomacromolecules, 2018Co-Authors: Arushi Prakash, Christopher J Mundy, Jim Pfaendtner, Marcel D BaerAbstract:Peptoids are peptide-mimetic biopolymers that are easy to synthesize and adaptable for use in drugs, chemical scaffolds, and coatings. However, there is insufficient information about their structural preferences and interactions with the environment in various applications. We conducted a study to understand the fundamental differences between peptides and Peptoids using molecular dynamics simulations with semiempirical (PM6) and empirical (AMBER) potentials, in conjunction with metadynamics enhanced sampling. From studies of single molecules in water and on surfaces, we found that sarcosine (model Peptoid) is much more flexible than alanine (model peptide) in different environments. However, the sarcosine and alanine interact similarly with a hydrophobic or a hydrophilic. Finally, this study highlights the conformational landscape of Peptoids and the dominant interactions that drive Peptoids toward these conformations.