{"bundle_type":"pith_open_graph_bundle","bundle_version":"1.0","pith_number":"pith:2025:L27EMZTHUERHEQPDS5Z5V4ALPR","short_pith_number":"pith:L27EMZTH","canonical_record":{"source":{"id":"2504.14722","kind":"arxiv","version":1},"metadata":{"license":"http://creativecommons.org/licenses/by-sa/4.0/","primary_cat":"physics.bio-ph","submitted_at":"2025-04-20T19:35:24Z","cross_cats_sorted":["cond-mat.soft","cond-mat.stat-mech","physics.chem-ph","physics.comp-ph"],"title_canon_sha256":"692de933b937f974e660526067ce7a29e4ef885843fe9c5ae1f988ac2a1fbcbb","abstract_canon_sha256":"0df6c36cddb075ef72f2c813df974e369a290787740b3559a4423a787bd84455"},"schema_version":"1.0"},"canonical_sha256":"5ebe466667a1227241e39773daf00b7c6ed9f636e021f6a025a7f43a8ce4da2c","source":{"kind":"arxiv","id":"2504.14722","version":1},"source_aliases":[{"alias_kind":"arxiv","alias_value":"2504.14722","created_at":"2026-07-05T11:09:11Z"},{"alias_kind":"arxiv_version","alias_value":"2504.14722v1","created_at":"2026-07-05T11:09:11Z"},{"alias_kind":"doi","alias_value":"10.48550/arxiv.2504.14722","created_at":"2026-07-05T11:09:11Z"},{"alias_kind":"pith_short_12","alias_value":"L27EMZTHUERH","created_at":"2026-07-05T11:09:11Z"},{"alias_kind":"pith_short_16","alias_value":"L27EMZTHUERHEQPD","created_at":"2026-07-05T11:09:11Z"},{"alias_kind":"pith_short_8","alias_value":"L27EMZTH","created_at":"2026-07-05T11:09:11Z"}],"events":[{"event_type":"record_created","subject_pith_number":"pith:2025:L27EMZTHUERHEQPDS5Z5V4ALPR","target":"record","payload":{"canonical_record":{"source":{"id":"2504.14722","kind":"arxiv","version":1},"metadata":{"license":"http://creativecommons.org/licenses/by-sa/4.0/","primary_cat":"physics.bio-ph","submitted_at":"2025-04-20T19:35:24Z","cross_cats_sorted":["cond-mat.soft","cond-mat.stat-mech","physics.chem-ph","physics.comp-ph"],"title_canon_sha256":"692de933b937f974e660526067ce7a29e4ef885843fe9c5ae1f988ac2a1fbcbb","abstract_canon_sha256":"0df6c36cddb075ef72f2c813df974e369a290787740b3559a4423a787bd84455"},"schema_version":"1.0"},"canonical_sha256":"5ebe466667a1227241e39773daf00b7c6ed9f636e021f6a025a7f43a8ce4da2c","receipt":{"kind":"pith_receipt","key_id":"pith-v1-2026-05","algorithm":"ed25519","signed_at":"2026-07-05T11:09:11.738592Z","signature_b64":"JIC6CakP1cWsOga7zcHmMdRHMjOPacEwWu8u95QntNX9yybcbskEE+ZYSbATxE3ozFTQijWJAYfq7oJvZYicBw==","signed_message":"canonical_sha256_bytes","builder_version":"pith-number-builder-2026-05-17-v1","receipt_version":"0.3","canonical_sha256":"5ebe466667a1227241e39773daf00b7c6ed9f636e021f6a025a7f43a8ce4da2c","last_reissued_at":"2026-07-05T11:09:11.738082Z","signature_status":"signed_v1","first_computed_at":"2026-07-05T11:09:11.738082Z","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54"},"source_kind":"arxiv","source_id":"2504.14722","source_version":1,"attestation_state":"computed"},"signer":{"signer_id":"pith.science","signer_type":"pith_registry","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54"},"created_at":"2026-07-05T11:09:11Z","supersedes":[],"prev_event":null,"signature":{"signature_status":"signed_v1","algorithm":"ed25519","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signature_b64":"L+bKHbN5pqZJtQ9KcluUqGbVCJM618otHYqDazD4xgBMi7m0+68DHi7XbQPbV+mYPgcN9lQIA5kk5i9aqeDqBQ==","signed_message":"open_graph_event_sha256_bytes","signed_at":"2026-08-23T10:01:35.815553Z"},"content_sha256":"ec2b626eb42dff623d7acd0f3117abb41dd800168c86eb41867275d8e8e73fb3","schema_version":"1.0","event_id":"sha256:ec2b626eb42dff623d7acd0f3117abb41dd800168c86eb41867275d8e8e73fb3"},{"event_type":"graph_snapshot","subject_pith_number":"pith:2025:L27EMZTHUERHEQPDS5Z5V4ALPR","target":"graph","payload":{"graph_snapshot":{"paper":{"title":"Path sampling challenges in large biomolecular systems: RETIS and REPPTIS for ABL-imatinib kinetics","license":"http://creativecommons.org/licenses/by-sa/4.0/","headline":"","cross_cats":["cond-mat.soft","cond-mat.stat-mech","physics.chem-ph","physics.comp-ph"],"primary_cat":"physics.bio-ph","authors_text":"An Ghysels, Daniel T. Zhang, Enrico Riccardi, Titus S. van Erp, Wouter Vervust","submitted_at":"2025-04-20T19:35:24Z","abstract_excerpt":"Predicting the kinetics of drug-protein interactions is crucial for understanding drug efficacy, particularly in personalized medicine, where protein mutations can significantly alter drug residence times. This study applies Replica Exchange Transition Interface Sampling (RETIS) and its Partial Path variant (REPPTIS) to investigate the dissociation kinetics of imatinib from Abelson nonreceptor tyrosine kinase (ABL) and mutants relevant to chronic myeloid leukemia therapy. These path-sampling methods offer a bias-free alternative to conventional approaches requiring qualitative predefined react"},"claims":{"count":0,"items":[],"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"source":{"id":"2504.14722","kind":"arxiv","version":1},"verdict":{"id":null,"model_set":{},"created_at":null,"strongest_claim":"","one_line_summary":"","pipeline_version":null,"weakest_assumption":"","pith_extraction_headline":""},"integrity":{"clean":true,"summary":{"advisory":0,"critical":0,"by_detector":{},"informational":0},"endpoint":"/pith/2504.14722/integrity.json","findings":[],"available":true,"detectors_run":[],"snapshot_sha256":"c28c3603d3b5d939e8dc4c7e95fa8dfce3d595e45f758748cecf8e644a296938"},"references":{"count":0,"sample":[],"resolved_work":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57","internal_anchors":0},"formal_canon":{"evidence_count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"author_claims":{"count":0,"strong_count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"builder_version":"pith-number-builder-2026-05-17-v1"},"verdict_id":null},"signer":{"signer_id":"pith.science","signer_type":"pith_registry","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54"},"created_at":"2026-07-05T11:09:11Z","supersedes":[],"prev_event":null,"signature":{"signature_status":"signed_v1","algorithm":"ed25519","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signature_b64":"4pvC1SjbVqmy8u6o8jYVd/7JWgFzpDEyWOBpXG+/oZCo76ew9ewLAJru526PTJuFri23Fgos457DQTKY3dmpCg==","signed_message":"open_graph_event_sha256_bytes","signed_at":"2026-08-23T10:01:35.816494Z"},"content_sha256":"04a3f0c46c4720f8140ea1c58350dacc6f68c25015c837bf475a6c843866952e","schema_version":"1.0","event_id":"sha256:04a3f0c46c4720f8140ea1c58350dacc6f68c25015c837bf475a6c843866952e"}],"timestamp_proofs":[],"mirror_hints":[{"mirror_type":"https","name":"Pith Resolver","base_url":"https://pith.science","bundle_url":"https://pith.science/pith/L27EMZTHUERHEQPDS5Z5V4ALPR/bundle.json","state_url":"https://pith.science/pith/L27EMZTHUERHEQPDS5Z5V4ALPR/state.json","well_known_bundle_url":"https://pith.science/.well-known/pith/L27EMZTHUERHEQPDS5Z5V4ALPR/bundle.json","status":"primary"}],"public_keys":[{"key_id":"pith-v1-2026-05","algorithm":"ed25519","format":"raw","public_key_b64":"stVStoiQhXFxp4s2pdzPNoqVNBMojDU/fJ2db5S3CbM=","public_key_hex":"b2d552b68890857171a78b36a5dccf368a953413288c353f7c9d9d6f94b709b3","fingerprint_sha256_b32_first128bits":"RVFV5Z2OI2J3ZUO7ERDEBCYNKS","fingerprint_sha256_hex":"8d4b5ee74e4693bcd1df2446408b0d54","rotates_at":null,"url":"https://pith.science/pith-signing-key.json","notes":"Pith uses this Ed25519 key to sign canonical record SHA-256 digests. Verify with: ed25519_verify(public_key, message=canonical_sha256_bytes, signature=base64decode(signature_b64))."}],"merge_version":"pith-open-graph-merge-v1","built_at":"2026-08-23T10:01:35Z","links":{"resolver":"https://pith.science/pith/L27EMZTHUERHEQPDS5Z5V4ALPR","bundle":"https://pith.science/pith/L27EMZTHUERHEQPDS5Z5V4ALPR/bundle.json","state":"https://pith.science/pith/L27EMZTHUERHEQPDS5Z5V4ALPR/state.json","well_known_bundle":"https://pith.science/.well-known/pith/L27EMZTHUERHEQPDS5Z5V4ALPR/bundle.json"},"state":{"state_type":"pith_open_graph_state","state_version":"1.0","pith_number":"pith:2025:L27EMZTHUERHEQPDS5Z5V4ALPR","merge_version":"pith-open-graph-merge-v1","event_count":2,"valid_event_count":2,"invalid_event_count":0,"equivocation_count":0,"current":{"canonical_record":{"metadata":{"abstract_canon_sha256":"0df6c36cddb075ef72f2c813df974e369a290787740b3559a4423a787bd84455","cross_cats_sorted":["cond-mat.soft","cond-mat.stat-mech","physics.chem-ph","physics.comp-ph"],"license":"http://creativecommons.org/licenses/by-sa/4.0/","primary_cat":"physics.bio-ph","submitted_at":"2025-04-20T19:35:24Z","title_canon_sha256":"692de933b937f974e660526067ce7a29e4ef885843fe9c5ae1f988ac2a1fbcbb"},"schema_version":"1.0","source":{"id":"2504.14722","kind":"arxiv","version":1}},"source_aliases":[{"alias_kind":"arxiv","alias_value":"2504.14722","created_at":"2026-07-05T11:09:11Z"},{"alias_kind":"arxiv_version","alias_value":"2504.14722v1","created_at":"2026-07-05T11:09:11Z"},{"alias_kind":"doi","alias_value":"10.48550/arxiv.2504.14722","created_at":"2026-07-05T11:09:11Z"},{"alias_kind":"pith_short_12","alias_value":"L27EMZTHUERH","created_at":"2026-07-05T11:09:11Z"},{"alias_kind":"pith_short_16","alias_value":"L27EMZTHUERHEQPD","created_at":"2026-07-05T11:09:11Z"},{"alias_kind":"pith_short_8","alias_value":"L27EMZTH","created_at":"2026-07-05T11:09:11Z"}],"graph_snapshots":[{"event_id":"sha256:04a3f0c46c4720f8140ea1c58350dacc6f68c25015c837bf475a6c843866952e","target":"graph","created_at":"2026-07-05T11:09:11Z","signer":{"key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signer_id":"pith.science","signer_type":"pith_registry"},"payload":{"graph_snapshot":{"author_claims":{"count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57","strong_count":0},"builder_version":"pith-number-builder-2026-05-17-v1","claims":{"count":0,"items":[],"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"formal_canon":{"evidence_count":0,"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"integrity":{"available":true,"clean":true,"detectors_run":[],"endpoint":"/pith/2504.14722/integrity.json","findings":[],"snapshot_sha256":"c28c3603d3b5d939e8dc4c7e95fa8dfce3d595e45f758748cecf8e644a296938","summary":{"advisory":0,"by_detector":{},"critical":0,"informational":0}},"paper":{"abstract_excerpt":"Predicting the kinetics of drug-protein interactions is crucial for understanding drug efficacy, particularly in personalized medicine, where protein mutations can significantly alter drug residence times. This study applies Replica Exchange Transition Interface Sampling (RETIS) and its Partial Path variant (REPPTIS) to investigate the dissociation kinetics of imatinib from Abelson nonreceptor tyrosine kinase (ABL) and mutants relevant to chronic myeloid leukemia therapy. These path-sampling methods offer a bias-free alternative to conventional approaches requiring qualitative predefined react","authors_text":"An Ghysels, Daniel T. Zhang, Enrico Riccardi, Titus S. van Erp, Wouter Vervust","cross_cats":["cond-mat.soft","cond-mat.stat-mech","physics.chem-ph","physics.comp-ph"],"headline":"","license":"http://creativecommons.org/licenses/by-sa/4.0/","primary_cat":"physics.bio-ph","submitted_at":"2025-04-20T19:35:24Z","title":"Path sampling challenges in large biomolecular systems: RETIS and REPPTIS for ABL-imatinib kinetics"},"references":{"count":0,"internal_anchors":0,"resolved_work":0,"sample":[],"snapshot_sha256":"258153158e38e3291e3d48162225fcdb2d5a3ed65a07baac614ab91432fd4f57"},"source":{"id":"2504.14722","kind":"arxiv","version":1},"verdict":{"created_at":null,"id":null,"model_set":{},"one_line_summary":"","pipeline_version":null,"pith_extraction_headline":"","strongest_claim":"","weakest_assumption":""}},"verdict_id":null}}],"author_attestations":[],"timestamp_anchors":[],"storage_attestations":[],"citation_signatures":[],"replication_records":[],"corrections":[],"mirror_hints":[],"record_created":{"event_id":"sha256:ec2b626eb42dff623d7acd0f3117abb41dd800168c86eb41867275d8e8e73fb3","target":"record","created_at":"2026-07-05T11:09:11Z","signer":{"key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signer_id":"pith.science","signer_type":"pith_registry"},"payload":{"attestation_state":"computed","canonical_record":{"metadata":{"abstract_canon_sha256":"0df6c36cddb075ef72f2c813df974e369a290787740b3559a4423a787bd84455","cross_cats_sorted":["cond-mat.soft","cond-mat.stat-mech","physics.chem-ph","physics.comp-ph"],"license":"http://creativecommons.org/licenses/by-sa/4.0/","primary_cat":"physics.bio-ph","submitted_at":"2025-04-20T19:35:24Z","title_canon_sha256":"692de933b937f974e660526067ce7a29e4ef885843fe9c5ae1f988ac2a1fbcbb"},"schema_version":"1.0","source":{"id":"2504.14722","kind":"arxiv","version":1}},"canonical_sha256":"5ebe466667a1227241e39773daf00b7c6ed9f636e021f6a025a7f43a8ce4da2c","receipt":{"algorithm":"ed25519","builder_version":"pith-number-builder-2026-05-17-v1","canonical_sha256":"5ebe466667a1227241e39773daf00b7c6ed9f636e021f6a025a7f43a8ce4da2c","first_computed_at":"2026-07-05T11:09:11.738082Z","key_id":"pith-v1-2026-05","kind":"pith_receipt","last_reissued_at":"2026-07-05T11:09:11.738082Z","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","receipt_version":"0.3","signature_b64":"JIC6CakP1cWsOga7zcHmMdRHMjOPacEwWu8u95QntNX9yybcbskEE+ZYSbATxE3ozFTQijWJAYfq7oJvZYicBw==","signature_status":"signed_v1","signed_at":"2026-07-05T11:09:11.738592Z","signed_message":"canonical_sha256_bytes"},"source_id":"2504.14722","source_kind":"arxiv","source_version":1}}},"equivocations":[],"invalid_events":[],"applied_event_ids":["sha256:ec2b626eb42dff623d7acd0f3117abb41dd800168c86eb41867275d8e8e73fb3","sha256:04a3f0c46c4720f8140ea1c58350dacc6f68c25015c837bf475a6c843866952e"],"state_sha256":"2eaf52b846f627acaf0e05976db391b9bb89ed562cfd6d4714c8971a81b7361e"},"bundle_signature":{"signature_status":"signed_v1","algorithm":"ed25519","key_id":"pith-v1-2026-05","public_key_fingerprint":"8d4b5ee74e4693bcd1df2446408b0d54","signature_b64":"3IZCTe3OLUANLV/6vs7r6EVIUKWnM+hKzcPLpHz2hsLCv+S7AZY8lCkcIcHjn8w8onwsUynzqR5urDy0MlYoCg==","signed_message":"bundle_sha256_bytes","signed_at":"2026-08-23T10:01:35.821995Z","bundle_sha256":"5377d2ae3d06e9b7781684628cb8088f509dac1a67314bd3b2dc220458d15fa3"}}