{"doi":"10.1021/acs.jpcb.4c00825","title":"Parallel β-Sheet Structure and Structural Heterogeneity Detected within Q11 Self-Assembling Peptide Nanofibers","abstract":"High Resolution Image Download MS PowerPoint Slide Q11 peptide nanofibers are used as a biomaterial for applications such as antigen presentation and tissue engineering, yet detailed knowledge of molecular-level structure has not been reported. The Q11 peptide sequence was designed using heuristics-based patterning of hydrophobic and polar amino acids with oppositely charged amino acids placed at opposite ends of the sequence to promote antiparallel β-sheet formation. In this work, we employed solid-state nuclear magnetic resonance spectroscopy (NMR) to evaluate whether the molecular organization within Q11 self-assembled peptide nanofibers is consistent with the expectations of the peptide designers. We discovered that Q11 forms a distribution of molecular structures. NMR data from two-dimensional (2D) 13 C– 13 C dipolar-assisted rotational resonance indicate that the K3 and E9 residues between Q11 β-strands are spatially proximate (within ∼0.6 nm). Frequency-selective rotational echo double resonance (fsREDOR) on K3 Nζ and E9 Cδ-labeled sites showed that approximately 9% of the sites are close enough for salt bridge formation to occur. Surprisingly, dipolar recoupling measurements revealed that Q11 peptides do not assemble into antiparallel β-sheets as expected, and structural analysis using Fourier-transform infrared spectroscopy and 2D NMR alone can be misleading. 13 C PITHIRDS-CT dipolar recoupling measurements showed that the most abundant structure consists of parallel β-sheets, in contrast to the expected antiparallel β-sheet structure. Structural heterogeneity was detected from 15 N{ 13 C} REDOR measurements, with approximately 22% of β-strands having antiparallel nearest neighbors. We cannot propose a complete structural model of Q11 nanofibers because of the complexity involved when examining structurally heterogeneous samples using NMR. Altogether, our results show that while heuristics-based patterning is effective in promoting β-sheet formation, designing a peptide sequence to form a targeted β-strand arrangement remains challenging.","journal":"The Journal of Physical Chemistry B","year":2024,"id":438421,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9599,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1084706,"name":"Kong M. Wong","orcid":"0000-0002-5298-3139","position":1,"is_corresponding":false},{"id":1070894,"name":"Johannes Leisen","orcid":"0000-0003-0474-670X","position":2,"is_corresponding":false},{"id":418757,"name":"Renjie Liu","orcid":"0000-0002-3885-244X","position":3,"is_corresponding":false},{"id":1248585,"name":"W. Radford","orcid":null,"position":4,"is_corresponding":false},{"id":1091967,"name":"Tarunya Rao Sudarshan","orcid":null,"position":5,"is_corresponding":false},{"id":418761,"name":"Gregory A. Hudalla","orcid":"0000-0003-2259-0809","position":6,"is_corresponding":false},{"id":580323,"name":"Anant K. Paravastu","orcid":"0000-0001-7183-1942","position":7,"is_corresponding":false},{"id":987526,"name":"Alicia S. Robang","orcid":"0000-0003-3857-9559","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T02:00:38.888629Z","pmid":"38787393","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}