Design of Protein Segments and Peptides for Binding to Protein Targets

Abstract

Recent years have witnessed a rise in methods for accurate prediction of structure and design of novel functional proteins. Design of functional protein fragments and peptides occupy a small, albeit unique, space within the general field of protein design. While the smaller size of these peptides allows for more exhaustive computational methods, flexibility in their structure and sparsity of data compared to proteins, as well as presence of noncanonical building blocks, add additional challenges to their design. This review summarizes the current advances in the design of protein fragments and peptides for binding to targets and discusses the challenges in the field, with an eye toward future directions.

Phosphate-binding protein-loaded iron oxide particles: adsorption performance for phosphorus removal and recovery from water

“…While the hinge motion is thus important, several studies provide substantial evidence supporting the feasibility of designing and synthesizing peptide sequences that leverage functional amino acid sequences derived from proteins. 64–66 For example, Fowler et al (2021) 67 demonstrated selective P i adsorption and controlled desorption using a protein-derived P i -binding peptide sequence approximately 37× smaller than the PBP tested in our study. Immobilization of such peptide sequences and testing their P i binding potential in a range of conditions relative to water/wastewater is important moving forward to further evaluate the adsorbent's abilities relative to other adsorbents.…”

Engineered Polypeptides as a Tool for Controlling Catalytic Active Janus Particles

“…98 Depending on the application, sequences that have already been discovered to have high affinity for a target can be utilized, iterated, or newly designed. 99 There is an opportunity in the active Janus particle community to utilize polypeptide specificity for biological targets, as well as utilize polypeptide affinity for solid materials including gold 100 and platinum. 101 For example, peptide-functionalized gold nanoparticles already serve as effective cell-targeting agents.…”

“…Sequences that can selectively bind to targets have been utilized for drug delivery, nanomaterial assembly, biosensing, and protein purification . Depending on the application, sequences that have already been discovered to have high affinity for a target can be utilized, iterated, or newly designed . There is an opportunity in the active Janus particle community to utilize polypeptide specificity for biological targets, as well as utilize polypeptide affinity for solid materials including gold and platinum .…”

Affinity Peptide-Tethered Suspension Hydrogel Sensor for Selective and Sensitive Detection of Influenza Virus

“…One of the successful strategies to design affinity peptides involves starting from a fragment or motif predicted to possess binding affinity and improving upon it. 29 Following phage display screening, the screened peptide sequences were analyzed to identify common patterns or motifs by examining specific amino acid residues. In this study, we aimed to enhance selectivity and sensitivity along with the application of hydrogel-based fluorescence sensors by designing and synthesizing new peptides based on motifs observed in C7Cmer 2R-17/12mer 3R-12 (motif 1, NXXNXLXW(F)) and 12mer 3R-21/12mer 4R-30 (motif 2, F(W)XY(S)XH-(K)SXXGAW).…”

“…Designing of H3N2 HA1 Targeted Peptide. One of the successful strategies to design affinity peptides involves starting from a fragment or motif predicted to possess binding affinity and improving upon it 29. Following phage display screening, the screened peptide sequences were analyzed to identify common patterns or motifs by examining specific amino acid residues.…”