{"doi":"10.1371/journal.pcbi.1002131","title":"Binding Free Energy Landscape of Domain-Peptide Interactions","abstract":null,"journal":"PLoS Computational Biology","year":2011,"id":679905,"datarank":0.4493598410330987,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.0,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1776450,"name":"Stefan Wallin","orcid":null,"position":1,"is_corresponding":false},{"id":1776448,"name":"Iskra Staneva","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Binding Free Energy Landscape of Domain-Peptide Interactions","abstract":"Peptide recognition domains (PRDs) are ubiquitous protein domains which mediate large numbers of protein interactions in the cell. How these PRDs are able to recognize peptide sequences in a rapid and specific manner is incompletely understood. We explore the peptide binding process of PDZ domains, a large PRD family, from an equilibrium perspective using an all-atom Monte Carlo (MC) approach. Our focus is two different PDZ domains representing two major PDZ classes, I and II. For both domains, a binding free energy surface with a strong bias toward the native bound state is found. Moreover, both domains exhibit a binding process in which the peptides are mostly either bound at the PDZ binding pocket or else interact little with the domain surface. Consistent with this, various binding observables show a temperature dependence well described by a simple two-state model. We also find important differences in the details between the two domains. While both domains exhibit well-defined binding free energy barriers, the class I barrier is significantly weaker than the one for class II. To probe this issue further, we apply our method to a PDZ domain with dual specificity for class I and II peptides, and find an analogous difference in their binding free energy barriers. Lastly, we perform a large number of fixed-temperature MC kinetics trajectories under binding conditions. These trajectories reveal significantly slower binding dynamics for the class II domain relative to class I. Our combined results are consistent with a binding mechanism in which the peptide C terminal residue binds in an initial, rate-limiting step.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21876662","pmcid":"PMC3158039","openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1002131&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pcbi.1002131","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3158039","host_type":"repository"},{"url":"https://doaj.org/article/56712f997269486cbed537dc48fc7246","host_type":"repository"},{"url":"https://figshare.com/articles/dataset/Binding_Free_Energy_Landscape_of_Domain_Peptide_Interactions/134107","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC3158039","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC3158039?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Computer Simulation","Humans","Kinetics","Models, Chemical","Models, Molecular","Monte Carlo Method","PDZ Domains","Peptides","Protein Binding","Protein Folding","Thermodynamics"],"mesh_terms":["Humans","Peptides","Monte Carlo Method","Protein Binding","Protein Folding","Kinetics","Thermodynamics","Models, Chemical","Models, Molecular","Computer Simulation","PDZ Domains"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T14:00:38.944423Z","pmid":null,"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":[]}