Three-dimensional Solution Structure Research Articles

Machine learning and genetic algorithm-guided directed evolution for the development of antimicrobial peptides

IntroductionAntimicrobial peptides (AMPs) are valuable alternatives to traditional antibiotics, possess a variety of potent biological activities and exhibit immunomodulatory effects that alleviate difficult-to-treat infections. Clarifying the structure-activity relationships of AMPs can direct the synthesis of desirable peptide therapeutics. ObjectivesIn this study, the lipopolysaccharide-binding domain (LBD) was identified through machine learning-guided directed evolution, which acts as a functional domain of the anti-lipopolysaccharide factor family of AMPs identified from Marsupenaeus japonicus. MethodsLBDA-D was identified as an output of this algorithm, in which the original LBDMj sequence was the input, and the three-dimensional solution structure of LBDB was determined using nuclear magnetic resonance. Furthermore, our study involved a comprehensive series of experiments, including morphological studies and in vitro and in vivo antibacterial tests. ResultsThe NMR solution structure showed that LBDB possesses a circular extended structure with a disulfide crosslink at the terminus and two 310-helices and exhibits a broad antimicrobial spectrum. In addition, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that LBDB induced the formation of a cluster of bacteria wrapped in a flexible coating that ruptured and consequently killed the bacteria. Finally, coinjection of LBDB, Vibrio alginolyticus and Staphylococcus aureus in vivo improved the survival of M. japonicus, demonstrating the promising therapeutic role of LBDB for treating infectious disease. ConclusionsThe findings of this study pave the way for the rational drug design of activity-enhanced peptide antibiotics.

On-Surface Synthesis of Multiple Cu Atom-Bridged Organometallic Oligomers.

A metal-metal bond between coordination complexes has the nature of a covalent bond in hydrocarbons. While bimetallic and trimetallic compounds usually have three-dimensional structures in solution, the high directionality and robustness of the bond can be applied for on-surface syntheses. Here, we present a systematic formation of complex organometallic oligomers on Cu(111) through sequential ring opening of 11,11,12,12-tetraphenyl-1,4,5,8-tetraazaanthraquinodimethane and bonding of phenanthroline derivatives by multiple Cu atoms. A detailed characterization with a combination of scanning tunneling microscopy and density functional theory calculations revealed the role of the Cu adatoms in both enantiomers of the chiral oligomers. Furthermore, we found sufficient strength of the bonds against sliding friction by manipulating the oligomers up to a hexamer. This finding may help to increase the variety of organometallic nanostructures on surfaces.

Structural Characterization of Food Allergens by Nuclear Magnetic Resonance Spectroscopy.

As allergies, especially those triggered by food, are becoming more and more prevalent, it is of increasing importance to fully understand the structures and dynamic behaviors of allergenic proteins along with their interactions with potential natural ligands. Therefore, we have established a solid routine to achieve structural characterization of food allergens, especially for birch pollen-related cross-reactive proteins from the class 10 of pathogenesis-related proteins (PR-10), by nuclear magnetic resonance (NMR) spectroscopy. Following expression of the desired allergen in Escherichia coli in isotope-labeled minimal media, the three-dimensional solution structures of these proteins can be determined, and insight into ligand binding mechanics and structural dynamic properties are accessible through NMR spin relaxation experiments.

Solution structure of the N-terminal extension domain of a Schistosoma japonicum asparaginyl-tRNA synthetase

Several secreted proteins from helminths (parasitic worms) have been shown to have immunomodulatory activities. Asparaginyl-tRNA synthetases are abundantly secreted in the filarial nematode Brugia malayi (BmAsnRS) and the parasitic flatworm Schistosoma japonicum (SjAsnRS), indicating a possible immune function. The suggestion is supported by BmAsnRS alleviating disease symptoms in a T-cell transfer mouse model of colitis. This immunomodulatory function is potentially related to an N-terminal extension domain present in eukaryotic AsnRS proteins but few structure/function studies have been done on this domain. Here we have determined the three-dimensional solution structure of the N-terminal extension domain of SjAsnRS. A protein containing the 114 N-terminal amino acids of SjAsnRS was recombinantly expressed with isotopic labelling to allow structure determination using 3D NMR spectroscopy, and analysis of dynamics using NMR relaxation experiments. Structural comparisons of the N-terminal extension domain of SjAsnRS with filarial and human homologues highlight a high degree of variability in the β-hairpin region of these eukaryotic N-AsnRS proteins, but similarities in the disorder of the C-terminal regions. Limitations in PrDOS-based intrinsically disordered region (IDR) model predictions were also evident in this comparison. Empirical structural data such as that presented in our study for N-SjAsnRS will enhance the prediction of sequence-homology based structure modelling and prediction of IDRs in the future. Communicated by Ramaswamy H. Sarma

Abstract A033: KRAS codon 12 oncogenic mutations modulate protein conformation within the Switch II/Helix3 pocket

Abstract Up to 30% of cancers harbor activating mutations in one of three RAS genes, HRAS, NRAS, or KRAS, that drive uncontrolled cellular proliferation, alter cellular metabolism, movement, differentiation, and promote cell survival and tumor immune evasion. The frequency of mutation varies across alleles and specific substitutions, with KRAS mutations occurring in roughly 81% of patients, and KRAS G12D, KRAS G12V, and KRAS G12C substitutions constituting 33%, 23%, and 12% of these cases, respectively. Cancer types exhibit characteristic preferences for RAS substitutions, the reason for which is still unknown. Oncogenic amino acid substitutions have been found to endow subtle differences in biochemical properties which cannot be explained by existing X-ray structural models. In addition, it is unclear whether these translate to distinctions in downstream signaling potential. We have initiated this study with the overall goal of understanding the effect of oncogenic mutations on the structure and dynamic properties of KRAS4b proteins in solution, and to identify any ensuing differences in effector binding behavior. Here, we present the data that identifies the structural differences between the common mutants KRAS G12D and KRAS G12C and the wildtype protein in the active conformation using solution-state NMR and Molecular Dynamics (MD) simulations, that could likely be coupled with the differing capacities to engage downstream effectors. Chemical shift perturbation (CSP) analysis demonstrates that oncogenic mutations in codon 12 of KRAS4b induce significant conformational differences when compared to the wildtype protein. These observations are localized to the Switch 2 region. We validate these observations in three-dimensional structures and reveal critical differences that are conferred by these oncogenic mutants. The solved three-dimensional solution structures of KRAS G12C/T35S/C118S-GppNHp and KRAS G12D/T35S/C118S-GppNHp reveal remarkable conformational differences within the Switch II regions, with the G12D-mutant protein adopting a relatively more flexible Switch II conformation than the G12C-mutant. Our MD simulations at a 2 µs timescale support these observations. Furthermore, we observed downstream signaling differences between KRAS G12C and KRAS G12D mutants in several cell line systems. If observed structural differences between KRAS mutants are found to directly translate to effector binding affinity, it would provide critical insight into why cancer types display preferences for RAS substitutions, and would inform RAS-targeted therapeutics. Citation Format: Brian Smith, Alok K. Sharma, Roger Ma, Megan Rigby, Vandana Kumari, Dominic Esposito, Dwight Nissley, Frank McCormick, Anna E. Maciag. KRAS codon 12 oncogenic mutations modulate protein conformation within the Switch II/Helix3 pocket [abstract]. In: Proceedings of the AACR Special Conference: Targeting RAS; 2023 Mar 5-8; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Res 2023;21(5_Suppl):Abstract nr A033.

Preparation of two-component polyacrylamide inverse emulsion drag reducer for slick water and investigation of its rheological and drag reduction properties

In this paper, a slick water drag reducer with excellent drag reduction and a simple molecular structure, called QIE-0, was prepared by inverse emulsion copolymerization. QIE-0 is a copolymer emulsion of acrylamide and 2-acrylamide-2-methylpropyl sulfonic acid with an average molecular weight of 5.17 × 106 Da. QIE-0 has excellent thermal stability, and the temperature resistance can reach 220 °C. Prolonged static storage (180 days) did not change the viscosity-increasing properties, and the viscosity of 0.1% QIE-0 solution is 5.2 mPa s. QIE-0 presents a three-dimensional network structure in an aqueous solution and the structure changes with concentration. QIE-0 has special fluidity and a linear viscoelastic domain from 0.1% to 100%. QIE-0 solution has no thixotropy and is a stable structure. The drag reduction rate of ultra-low concentration (0.01%) slick water systems reaches 82.10%. The drag reduction rates of different systems are fitted by the established exponential function model and the power function model, and the correlation coefficient between the predicted values and the experimental values is greater than 0.999. QIE-0 meets the needs of slick water fracturing fluid applications and has huge potential applications in unconventional oil and gas production.

A Model for the Rapid Assessment of Solution Structures for 24-Atom Macrocycles: The Impact of β-Branched Amino Acids on Conformation.

Experiment and computation are used to develop a model to rapidly predict solution structures of macrocycles sharing the same Murcko framework. These 24-atom triazine macrocycles result from the quantitative dimerization of identical monomers presenting a hydrazine group and an acetal tethered to an amino acid linker. Monomers comprising glycine and the β-branched amino acids threonine, valine, and isoleucine yield macrocycles G-G, T-T, V-V, and I-I, respectively. Elements common to all members of the framework include the efficiency of macrocyclization (quantitative), the solution- and solid-state structures (folded), the site of protonation (opposite the auxiliary dimethylamine group), the geometry of the hydrazone (E), the C2 symmetry of the subunits (conserved), and the rotamer state adopted. In aggregate, the data reveal metrics predictive of the three-dimensional solution structure that derive from the fingerprint region of the 1D 1H spectrum and a network of rOes from a single resonance. The metrics also afford delineation of more nuanced structural features that allow subpopulations to be identified among the members of the framework. Well-tempered metadynamics provides free energy surfaces and population distributions of these macrocycles. The areas of the free energy surface decrease with increasing steric bulk (G-G > V-V ∼ T-T > I-I). In addition, the surfaces are increasingly isoenergetic with decreasing steric bulk (G-G > V-V ∼ T-T > I-I).

Synthetic Approaches to Break the Chemical Shift Degeneracy of Glycans.

NMR spectroscopy is the leading technique for determining glycans' three-dimensional structure and dynamic in solution as well as a fundamental tool to study protein-glycan interactions. To overcome the severe chemical shift degeneracy of these compounds, synthetic probes carrying NMR-active nuclei (e. g., 13 C or 19 F) or lanthanide tags have been proposed. These elegant strategies permitted to simplify the complex NMR analysis of unlabeled analogues, shining light on glycans' conformational aspects and interaction with proteins. Here, we highlight some key achievements in the synthesis of specifically labeled glycan probes and their contribution towards the fundamental understanding of glycans.

The acyclotide ribe 31 from Rinorea bengalensis has selective cytotoxicity and potent insecticidal properties in Drosophila

Cyclotides and acyclic versions of cyclotides (acyclotides) are peptides involved in plant defense. These peptides contain a cystine knot motif formed by three interlocked disulfide bonds, with the main difference between the two classes being the presence or absence of a cyclic backbone, respectively. The insecticidal activity of cyclotides is well documented, but no study to date explores the insecticidal activity of acyclotides. Here, we present the first in vivo evaluation of the insecticidal activity of acyclotides from Rinorea bengalensis on the vinegar fly Drosophila melanogaster. Of a group of structurally comparable acyclotides, ribe 31 showed the most potent toxicity when fed to D. melanogaster. We screened a range of acyclotides and cyclotides and found their toxicity toward human red blood cells was substantially lower than toward insect cells, highlighting their selectivity and potential for use as bioinsecticides. Our confocal microscopy experiments indicated their cytotoxicity is likely mediated via membrane disruption. Furthermore, our surface plasmon resonance studies suggested ribe 31 preferentially binds to membranes containing phospholipids with phosphatidyl-ethanolamine headgroups. Despite having an acyclic backbone, we determined the three-dimensional NMR solution structure of ribe 31 is similar to that of cyclotides. In summary, our results suggest that, with further optimization, ribe 31 could have applications as an insecticide due to its potent in vivo activity against D. melanogaster. More broadly, this work advances the field by demonstrating that acyclotides are more common than previously thought, have potent insecticidal activity, and have the advantage of potentially being more easily manufactured than cyclotides.

From dilute to concentrated solutions of intrinsically disordered proteins: Sample preparation and data collection.

It is well-known that an increasing proportion of proteins, protein regions, and partners of globular proteins are being recognized as having an intrinsic disorder, and therefore, not adopting a single three-dimensional structure in solution. For these proteins, small-angle X-ray scattering (SAXS) has become a premier method for examination, since it can provide information about the ensemble of the structural conformations as well as the intermolecular interactions. SAXS measurements can be performed from low to high protein concentrations under different physicochemical properties of the solution. The focus of this chapter is to introduce the basics of how to use SAXS for protein samples, for new and less experienced users, in a simple and concise manner, with emphasis on highly flexible proteins and regions. Methodological aspects in the sample preparation, experiment design, and data collection stages are raised that should be considered prior to attempting SAXS experiments. This is to ensure that high-quality SAXS data is obtained that enables accurate analysis. However, many of the points raised will also be worth considering for SAXS experiments of globular proteins.

Double Proton Transfer during a Novel Tertiary α-Ketol Rearrangement in Ketol-Acid Reductoisomerase: A Water-Mediated, Metal-Catalyzed, Base-Induced Mechanism.

(KARI) catalyzes the conversion of (S)-2-acetolactate or (S)-2-aceto-2-hydroxybutyrate to 2,3-dihydroxy-3-alkylbutyrate, the second step in the biosynthesis of branched chain amino acids (BCAAs). Because the BCAA biosynthetic pathway is present in bacteria, plants, and fungi, but absent in animals, it is an excellent target for the development of new-generation antibiotics and herbicides. Nevertheless, the mechanism of the KARI-catalyzed reaction has not yet been fully solved. In this study, we used iterative molecular dynamics (MD) flexible fitting-Rosetta techniques to optimize the three-dimensional solution structure of archaea KARI from Sulfolobus solfataricus (Sso-KARI) determined from cryo-electron microscopy. On the basis of the structure of the Sso-KARI/2Mg2+/NADH/(S)-2-acetolactate complex, we deciphered the catalytic mechanism of the KARI-mediated reaction through hybrid quantum mechanics/molecular mechanics MD simulations in conjunction with umbrella sampling. With an activation energy of only 6.06 kcal/mol, a water-mediated, metal-catalyzed, base-induced (WMMCBI) mechanism was preferred for deprotonation of the tertiary OH group of (S)-2-acetolactate in Sso-KARI. The WMMCBI mechanism for double proton transfer occurred within a proton wire route with two steps involving the formation of hydroxide: (i) Glu233 served as a general base to deprotonate the Mg2+-bound water, forming a hydroxide-coordinated Mg2+ ion; (ii) this hydroxide ion acted as a strong base that rapidly deprotonated the ternary OH group of the substrate. In contrast, the direct deprotonation of the substrate by Glu233 was kinetically unfavorable. This mechanism suggests a novel approach for designing catalysts for deprotonation and provides clues for the development of new-generation antibiotics and herbicides.

Structure and Zeatin Binding of the Peach Allergen Pru p 1.

Peach (Prunus persica) is among the fruits most frequently reported to cause food allergies. Allergic reactions commonly result from previous sensitization to the birch pollen allergen Bet v 1, followed by immunological cross-reactivity of IgE antibodies to structurally related proteins in peach. In this study, we present the three-dimensional NMR solution structure of the cross-reactive peach allergen Pru p 1 (isoform Pru p 1.0101). This 17.5 kDa protein adopts the canonical Bet v 1 fold, composed of a seven-stranded β-sheet and three α-helices enclosing an internal cavity. In Pru p 1, the inner surface of the cavity contains an array of hydroxyl-bearing amino acids surrounded by a hydrophobic patch, constituting a docking site for amphiphilic molecules. NMR-guided docking of the cytokinin molecule zeatin to the internal cavity of Pru p 1 provides a structure-based rationale for the effect that zeatin binding has on the protein’s RNase activity.

NMR resonance assignments of the PR-10 allergens Act c 8 and Act d 8 from golden and green kiwifruit

Kiwifruits have become one of the most common food sources triggering allergic reactions. In patients suffering from birch pollen related food allergy, reactions result from initial sensitization to the birch (Betula verrucosa) pollen allergen Bet v 1, followed by immunological cross-reactivity to structurally homologous proteins in kiwifruit. Clinical symptoms range from scratching and itching of the oral cavity to more severe immunological reactions such as rhino conjunctivitis. In this work we assigned backbone and side chain 1H, 13C and 15N chemical shifts of the 17 kDa PR-10 allergens Act c 8.0101 and Act d 8.0101 from golden (Actinidia chinesis) and green (Actinidia deliciosa) kiwifruit by solution NMR spectroscopy. The chemical shift data confirm the characteristic Bet v 1 fold for both proteins, consisting of a seven-stranded antiparallel β-sheet interrupted by two short α-helices, along with a long C-terminal α-helix. Our data provide the basis for determining the three-dimensional solution structures of these proteins and characterizing their immunological cross-reactivity on a structural basis.

Exploring the conformational dynamics and flexibility of intrinsically disordered HIV-1 Nef protein using molecular dynamic network approaches.

The online version contains supplementary material available at 10.1007/s13205-021-02698-8.

Towards an understanding of the role of intrinsic protein disorder on plant adaptation to environmental challenges.

Intrinsic protein disorder is an interesting structural feature where fully functional proteins lack a three-dimensional structure in solution. In this work, we estimated the relative content of intrinsic protein disorder in 96 plant proteomes including monocots and eudicots. In this analysis, we found variation in the relative abundance of intrinsic protein disorder among these major clades; the relative level of disorder is higher in monocots than eudicots. In turn, there is an inverse relationship between the degree of intrinsic protein disorder and protein length, with smaller proteins being more disordered. The relative abundance of amino acids depends on intrinsic disorder and also varies among clades. Within the nucleus, intrinsically disordered proteins are more abundant than ordered proteins. Intrinsically disordered proteins are specialized in regulatory functions, nucleic acid binding, RNA processing, and in response to environmental stimuli. The implications of this on plants' responses to their environment are discussed.

Unique β-Turn Peptoid Structures and Their Application as Asymmetric Catalysts.

Peptoids, N-substituted glycine oligomers, represent an important class of peptidomimetics that can fold into three-dimensional structures in solution. Most of the folded peptoid structures, however, resemble helices, and this can limit their applications, specifically in asymmetric catalysis. In this work, for the first time, unique examples of pyrrolidine-based β-turn-like peptoids are described and characterized, both in the solid state, by single-crystal X-ray analysis, and in solution, by circular dichroism spectroscopy. Furthermore, their highly efficient and enantioselective catalytic activity for the production of γ-nitro aldehydes by asymmetric Michael reaction in water was demonstrated. The structural properties and DFT-D3 calculations of the new β-turn-like peptoids, as well as catalytic and spectroscopic studies on designed pyrrolidine-based helical peptoids, suggest that the β-turn structure plays a key role in the stereoselectivity of the catalytic reaction.

Pharmacological activity and NMR solution structure of the leech peptide HSTX-I

The role of voltage-gated sodium (NaV) channels in pain perception is indisputable. Of particular interest as targets for the development of pain therapeutics are the tetrodotoxin-resistant isoforms NaV1.8 and NaV1.9, based on animal as well as human genetic studies linking these ion channel subtypes to the pathogenesis of pain. However, only a limited number of inhibitors selectively targeting these channels have been reported. HSTX-I is a peptide toxin identified from saliva of the leech Haemadipsa sylvestris. The native 23-residue peptide, stabilised by two disulfide bonds, has been reported to inhibit rat NaV1.8 and mouse NaV1.9 with low micromolar activity, and may therefore represent a scaffold for development of novel modulators with activity at human tetrodotoxin-resistant NaV isoforms. We synthetically produced this hydrophobic peptide in high yield using a one-pot oxidation and single step purification and determined the three-dimensional solution structure of HSTX-I using NMR solution spectroscopy. However, in our hands, the synthetic HSTX-I displayed only very modest activity at human NaV1.8 and NaV1.9, and lacked analgesic efficacy in a murine model of inflammatory pain.

Localized High Concentration Electrolytes for High Voltage Lithium-Metal Batteries: Correlation between Salt, Solvent, and Diluent Contents, and Reductive Stability of the Electrolytes

The quest for energy storage devices with high energy densities leads researches to drift away from conventional electrodes for novel architectures able to withstand high lithium loadings and deliver high discharge voltages. Two of the most promising electrode architectures to achieve these goals are the lithium metal anodes and the so-called high-Ni LiNixCoyMn1-x-yO2 (x ≥ 0.6) (NMC) cathodes based on mixed transition metal oxides. These electrodes, however, produce strong reducing/oxidizing environments at the interface with the electrolyte. Dilute electrolyte formulations (dominant in conventional lithium-ion batteries) are inadequate to resist uncontrolled electrolyte decomposition, triggering Li dendritic growth, and prompting low Coulombic efficiency (CE).There is an urgent need to work on new electrolyte formulations. In this sense, high concentrated electrolytes (HCE) gained attention due to their enhanced reductive and oxidative stability and high carrier density but still suffer from low ionic conductivity, high viscosity, and poor wettability. A promising strategy to overcome these drawbacks is diluting the electrolyte without affecting the original lithium salt – solvent coordination from the HCE, which has proven effective in increasing the CE and producing thinner lithium deposition patterns on the anode compared to dilute electrolytes.In this work, we examine the liquid structure and electronic properties in dilute, HCE, and localized high concentration electrolytes (LHCE), in an attempt to uncover changes in the solvated complexes based on salt, solvent, and diluent contents, focusing on an electrolyte formulation proven effective in experiments with lithium bis(fluorosulfonyl)imide (LiFSI), dimethyl carbonate (DMC), and bis(2,2,2-triflouroethyl) ether (BTFE) as the diluent. In our calculations, we modeled the liquid electrolytes within a unit cell with periodic boundaries along the x-, y-, and z-coordinates, and followed the formation of solvated structures performing ab-initio molecular dynamics (AIMD).Examining the dilute and the HCE formulations, besides the depletion of free solvent DMC molecules, we found a change in the coordination behavior of the FSI- anions that trigger the formation of a three-dimensional solution structure. Each FSI- anion coordinates with multiple lithium-ions, shifting the anion LUMO levels lower than the solvent molecules, which explains the improved reductive stability of the HCE formulation and the salt-dominant composition of the SEI films in experiments. Different from previous explanations, however, we do not attribute this improvement to the depletion of free solvent molecules but to lithium-salt pairing mechanisms modified in HCE electrolytes.For the LHCE formulations, we found that dilution does not influence the three-dimensional solution structure from the equivalent HCE. However, we found there should be a limit beyond which the solvation complexes that exist in the equivalent HCE formulation disappear. In summary, our approach allows for the development of a screening methodology that allows finding a correlation between the salt, solvent, and diluent contents, and the reductive properties of the electrolyte formulation. We believe this methodology constitutes an effective tool to explore further LHCE electrolyte formulations for a new generation of high energy density rechargeable batteries.

Intragenic antimicrobial peptides (IAPs) from human proteins with potent antimicrobial and anti-inflammatory activity.

Following the treads of our previous works on the unveiling of bioactive peptides encrypted in plant proteins from diverse species, the present manuscript reports the occurrence of four proof-of-concept intragenic antimicrobial peptides in human proteins, named Hs IAPs. These IAPs were prospected using the software Kamal, synthesized by solid phase chemistry, and had their interactions with model phospholipid vesicles investigated by differential scanning calorimetry and circular dichroism. Their antimicrobial activity against bacteria, yeasts and filamentous fungi was determined, along with their cytotoxicity towards erythrocytes. Our data demonstrates that Hs IAPs are capable to bind model membranes while attaining α-helical structure, and to inhibit the growth of microorganisms at concentrations as low as 1μM. Hs02, a novel sixteen residue long internal peptide (KWAVRIIRKFIKGFIS-NH2) derived from the unconventional myosin 1h protein, was further investigated in its capacity to inhibit lipopolysaccharide-induced release of TNF-α in murine macrophages. Hs02 presented potent anti-inflammatory activity, inhibiting the release of TNF-α in LPS-primed cells at the lowest assayed concentration, 0.1 μM. A three-dimensional solution structure of Hs02 bound to DPC micelles was determined by Nuclear Magnetic Resonance. Our work exemplifies how the human genome can be mined for molecules with biotechnological potential in human health and demonstrates that IAPs are actual alternatives to antimicrobial peptides as pharmaceutical agents or in their many other putative applications.

Biomolecules Turn Self-Assembling Amphiphilic Block Co-polymer Platforms Into Biomimetic Interfaces.

Biological membranes constitute an interface between cells and their surroundings and form distinct compartments within the cell. They also host a variety of biomolecules that carry out vital functions including selective transport, signal transduction and cell-cell communication. Due to the vast complexity and versatility of the different membranes, there is a critical need for simplified and specific model membrane platforms to explore the behaviors of individual biomolecules while preserving their intrinsic function. Information obtained from model membrane platforms should make invaluable contributions to current and emerging technologies in biotechnology, nanotechnology and medicine. Amphiphilic block co-polymers are ideal building blocks to create model membrane platforms with enhanced stability and robustness. They form various supramolecular assemblies, ranging from three-dimensional structures (e.g., micelles, nanoparticles, or vesicles) in aqueous solution to planar polymer membranes on solid supports (e.g., polymer cushioned/tethered membranes,) and membrane-like polymer brushes. Furthermore, polymer micelles and polymersomes can also be immobilized on solid supports to take advantage of a wide range of surface sensitive analytical tools. In this review article, we focus on self-assembled amphiphilic block copolymer platforms that are hosting biomolecules. We present different strategies for harnessing polymer platforms with biomolecules either by integrating proteins or peptides into assemblies or by attaching proteins or DNA to their surface. We will discuss how to obtain synthetic structures on solid supports and their characterization using different surface sensitive analytical tools. Finally, we highlight present and future perspectives of polymer micelles and polymersomes for biomedical applications and those of solid-supported polymer membranes for biosensing.