Sequence–Conformation Relationship of Zwitterionic Peptide Brushes: Theories and Simulations

Abstract

Zwitterionic polymer brushes have broad applications in antifouling, biolubrication, and drug delivery. The charge distribution on polymers is critical to the structure and properties of surface-tethered zwitterionic polymer brushes. However, there is a lack of understanding of the relationship between the charge distribution and conformation in these systems, which is important for designing and predicting the functionality of controllable surface-tethered polymer brushes. Zwitterionic peptides with different sequences of charged amino acids are excellent model systems to elucidate such a charge–conformation relationship. By performing all-atom molecular dynamics (MD) simulations and developing a discrete-charge mean-field theory, we perform a systematic investigation on the effect of charge distribution on the conformations of zwitterionic peptide brushes. All-atom MD simulations reveal that the height of the peptide brush strongly depends on the distribution of the charges along the peptide chain. Contact map analysis reveals that the charge sequence also determines the preferred intrachain (loops and extended) and interchain (head-to-tail and parallel) structures. Through the theory developed by us, we show that the interchain electrostatic interactions are responsible for the contraction of peptide brushes with long charged blocks, while elasticity drives the contraction of peptide brushes with alternating-charged segments. This study provides a clear illustration of the factors influencing the sequence–conformation relationship of zwitterionic peptide brushes.

Designed Polyhydroxyproline Helical Peptide with Ultrarobust Antifouling Capability for Electrochemical Sensing in Diverse Complex Biological Fluids

“…The MD simulations (Figures S1 and S2) revealed that PHHP maintains a more stable secondary structure compared to ZIP, as supported by residue contact maps and the Ramachandran plot (Figures S3 and S4), indicating that the unique polyhydroxyproline helical structure of PHHP effectively retains its rigidity, while ZIP tends to adopt folded and disordered conformations due to its flexibility. 5,17 Furthermore, a 100 ns MD simulation (Figures S5 and S6) affirmed that PHHP exhibits a stable backbone with minimal fluctuations, while ZIP demonstrates structural instability and higher flexibility, especially in its terminal residues, consistent with previous observations. 7 The hydrophilicity of a peptide is critical in assessing its antifouling effect, as it affects the formation of the protective hydration layer.…”

“…The presence of salt bridges served as an indication of the potential impact of ion− peptide interactions on the peptide's overall behavior and characteristics, encompassing electrical properties and structure, surpassing simple adsorption. 17 Indeed, the analysis of the adsorption of Fe 3+ with ZIP indicated that the strongest adsorption occurs due to coordination interactions between Fe 3+ and the carboxyl groups of the peptide. This coordination interaction was visually represented in Figure S11D, highlighting the specific binding sites and the formation of coordination complexes between Fe 3+ ions and the carboxyl groups in ZIP.…”

“…Additionally, in Figure E,F, an intriguing observation was made regarding the formation of the additional salt bridge, which was established through the interaction between Ca 2+ and SO 4 2– with multiple groups of ZIP. The presence of salt bridges served as an indication of the potential impact of ion–peptide interactions on the peptide’s overall behavior and characteristics, encompassing electrical properties and structure, surpassing simple adsorption …”

Anti‐Fouling Polymer or Peptide‐Modified Electrochemical Biosensors for Improved Biosensing in Complex Media

“…Blockcharged peptides prefer loop and head-to-tail structures upon surface attachment whereas alternating-charged peptide prefer extended and parallel structures with dense brush structures; consequently, alternately-charged peptides performed better in antifouling applications. [55] Peptides can also be tuned to bind to specific targets via the use of biorecognition sequences, including specific types of polymers or other biomaterials relevant for surface functionalization to create a more stable anti-fouling layer than would be achieved by simple physicochemical interactions. For example, Date et al used a polyetherimide-specific polymer-binding peptide to observe the effect of peptide density on the further attachment of functional proteins to the surface.…”

pH response of sequence-controlled polyampholyte brushes

“…21 Various computational and theoretical approaches have been applied to investigate the influence of monomer sequence and other variables on the properties of PABs. [22][23][24][25][26] However, these studies have focused on sequence-controlled PABs with strong acid and base chemistries in which the monomers remain fully ionized under typical solution conditions or employed methods that assume fixed monomer charge states. By contrast, PABs with weakly acidic and basic monomers exhibit changes in their charge state due to variations in pH a Department of Chemical and Biomolecular Engineering, University of Houston, and salt concentration and hence enhanced brush responses that can be harnessed to design smart surfaces.…”