{"doi":"10.1021/acs.jctc.5c00459","title":"MSBack: Multiscale Backmapping of Highly Coarse-Grained Proteins Using Constrained Diffusion","abstract":"Coarse-grained (CG) molecular dynamics is a powerful tool for simulating the collective behavior of biomolecules. However, the structural information lost during coarse-graining prevents the CG configurations from being more widely useful (e.g., for ligand binding). Regenerating the lost all-atom coordinates, or backmapping, is an unmet challenge for protein CG at resolutions lower than one coarse-grain site or bead per amino acid residue. This low resolution is computationally necessary to simulate many protein complexes including viruses like SARS-CoV-2 and HIV-1. We propose MSBack, a method to backmap highly CG proteins using a diffusion model for the all-atom coordinates constrained to fit the CG coordinates. This diffusion process works by perturbing a known all-atom structure and does not require retraining. We show that this stochastically generates a distribution of α-carbon traces that match the CG coordinates. By combining this with physics-based methods for smaller-length backmapping, we fully backmap a mature HIV-1 capsid bound with the small molecule inositol hexakisphosphate at 1 Å resolution.","journal":"Journal of Chemical Theory and Computation","year":2025,"id":517466,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":822211,"name":"Yihang Wang","orcid":"0000-0002-3566-2042","position":1,"is_corresponding":false},{"id":1383772,"name":"Chengxi Yang","orcid":"0000-0002-6209-0473","position":2,"is_corresponding":false},{"id":287970,"name":"Siyoung Kim","orcid":"0000-0003-4670-9747","position":3,"is_corresponding":false},{"id":246697,"name":"Gregory A. Voth","orcid":"0000-0002-3267-6748","position":4,"is_corresponding":false},{"id":832277,"name":"Curt Waltmann","orcid":"0000-0001-7029-214X","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:48:59.410472Z","pmid":"40452189","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":[]}