Predicting the structural basis of targeted protein degradation by integrating molecular dynamics simulations with structural mass spectrometry.

Dixon T, MacPherson D, Mostofian B, Dauzhenka T, Lotz S, McGee D, Shechter S, Shrestha UR, Wiewiora R, McDargh ZA, Pei F, Pal R, Ribeiro JV, Wilkerson T, Sachdeva V, Gao N, Jain S, Sparks S, Li Y, Vinitsky A, Zhang X, Razavi AM, Kolossváry I, Imbriglio J, Evdokimov A, Bergeron L, Zhou W, Adhikari J, Ruprecht B, Dickson A, Xu H, Sherman W, Izaguirre JA
Nat Commun 13(1):5884 (2022 Oct 6)

PMID: 36202813 doi: 10.1038/s41467-022-33575-4

Submitted to SASBDB: 2022 Aug 18 Published in SASBDB: 2022 Sep 15

SASDPE8 – SMARCA2 bromodomain (isoform1):Protac (ACBI1):VCB (VHL-elongin C-elongin B) Sample: Probable global transcription activator SNF2L2 (isoform 1) monomer, 16 kDa Homo sapiens protein Von Hippel-Lindau disease tumor suppressor monomer, 19 kDa Homo sapiens protein Elongin-B monomer, 12 kDa Homo sapiens protein Elongin-C monomer, 11 kDa Homo sapiens protein ACBI1 protac monomer, 1 kDa Buffer: 20 mM HEPES, 150 mM NaCl, 1 mM DTT, pH: 7.5 Experiment: SAXS data collected at Xenocs BioXolver L with MetalJet, Département de Biochimie, Université de Montréal on 2021 Aug 11 RgGuinier 3.3 nm Dmax 12.5 nm VolumePorod 83 nm3

SASDPF8 – SMARCA2 bromodomain (isoform2):Protac (ACBI1):VCB (VHL-elongin C-elongin B) Sample: Von Hippel-Lindau disease tumor suppressor monomer, 19 kDa Homo sapiens protein Elongin-B monomer, 12 kDa Homo sapiens protein Elongin-C monomer, 11 kDa Homo sapiens protein ACBI1 protac monomer, 1 kDa Probable global transcription activator SNF2L2 (isoform 2) monomer, 14 kDa Homo sapiens protein Buffer: 20 mM HEPES, 150 mM NaCl, 1 mM DTT, pH: 7.5 Experiment: SAXS data collected at Xenocs BioXolver L with MetalJet, Département de Biochimie, Université de Montréal on 2021 Aug 11 RgGuinier 3.2 nm Dmax 11.1 nm VolumePorod 75 nm3