caa a22 4500 445325917 CHVBK 20180317142720.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s10858-011-9522-4 doi (NATIONALLICENCE)springer-10.1007/s10858-011-9522-4 Protein side-chain resonance assignment and NOE assignment using RDC-defined backbones without TOCSY data [Elektronische Daten] [Jianyang Zeng, Pei Zhou, Bruce Donald] One bottleneck in NMR structure determination lies in the laborious and time-consuming process of side-chain resonance and NOE assignments. Compared to the well-studied backbone resonance assignment problem, automated side-chain resonance and NOE assignments are relatively less explored. Most NOE assignment algorithms require nearly complete side-chain resonance assignments from a series of through-bond experiments such as HCCH-TOCSY or HCCCONH. Unfortunately, these TOCSY experiments perform poorly on large proteins. To overcome this deficiency, we present a novel algorithm, called Nasca (NOE Assignment and Side-Chain Assignment), to automate both side-chain resonance and NOE assignments and to perform high-resolution protein structure determination in the absence of any explicit through-bond experiment to facilitate side-chain resonance assignment, such as HCCH-TOCSY. After casting the assignment problem into a Markov Random Field (MRF), Nasca extends and applies combinatorial protein design algorithms to compute optimal assignments that best interpret the NMR data. The MRF captures the contact map information of the protein derived from NOESY spectra, exploits the backbone structural information determined by RDCs, and considers all possible side-chain rotamers. The complexity of the combinatorial search is reduced by using a dead-end elimination (DEE) algorithm, which prunes side-chain resonance assignments that are provably not part of the optimal solution. Then an A* search algorithm is employed to find a set of optimal side-chain resonance assignments that best fit the NMR data. These side-chain resonance assignments are then used to resolve the NOE assignment ambiguity and compute high-resolution protein structures. Tests on five proteins show that Nasca assigns resonances for more than 90% of side-chain protons, and achieves about 80% correct assignments. The final structures computed using the NOE distance restraints assigned by Nasca have backbone RMSD 0.8-1.5Å from the reference structures determined by traditional NMR approaches. Springer Science+Business Media B.V., 2011 Nuclear magnetic resonance (NMR) nationallicence Side-chain resonance assignment nationallicence Nuclear Overhauser effect (NOE) assignment nationallicence Residual dipolar coupling (RDC) nationallicence Protein structure determination nationallicence NMR : Nuclear magnetic resonance nationallicence ppm : Parts per million nationallicence RMSD : Root mean square deviation nationallicence HSQC : Heteronuclear single quantum coherence spectroscopy nationallicence NOE : Nuclear Overhauser effect nationallicence NOESY : Nuclear Overhauser and exchange spectroscopy nationallicence TOCSY : Total correlation spectroscopy nationallicence TROSY : Transverse relaxation-optimized spectroscopy nationallicence RDC : Residual dipolar coupling nationallicence PDB : Protein Data Bank nationallicence BMRB : Biological Magnetic Resonance Bank nationallicence pol η UBZ : Ubiquitin-binding zinc finger domain of the human Y-family DNA polymerase Eta nationallicence hSRI : Human Set2-Rpb1 interacting domain nationallicence FF2 : FF Domain 2 of human transcription elongation factor CA150 nationallicence GB1 : B1 domain of Protein G nationallicence CH : Cα−Hα nationallicence SSE : Secondary structure element nationallicence $$\hbox{C}^{\prime}$$ : Carbonyl carbon nationallicence MRF : Markov Random Field nationallicence DEE : Dead-end elimination nationallicence GMEC : Global minimum energy conformation nationallicence SA : Simulated annealing nationallicence MD : Molecular dynamics nationallicence $${\mathbb{R}}^3$$ : 3-Dimensional Euclidean space nationallicence Zeng Jianyang Department of Computer Science, Duke University, 27708, Durham, NC, USA aut Zhou Pei Department of Biochemistry, Duke University Medical Center, 27710, Durham, NC, USA aut Donald Bruce Department of Computer Science, Duke University, 27708, Durham, NC, USA aut Journal of Biomolecular NMR Springer Netherlands 50/4(2011-08-01), 371-395 0925-2738 50:4<371 2011 50 10858 https://doi.org/10.1007/s10858-011-9522-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10858-011-9522-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zeng Jianyang Department of Computer Science, Duke University, 27708, Durham, NC, USA aut NATIONALLICENCE 700 1- Zhou Pei Department of Biochemistry, Duke University Medical Center, 27710, Durham, NC, USA aut NATIONALLICENCE 700 1- Donald Bruce Department of Computer Science, Duke University, 27708, Durham, NC, USA aut NATIONALLICENCE 773 0- Journal of Biomolecular NMR Springer Netherlands 50/4(2011-08-01), 371-395 0925-2738 50:4<371 2011 50 10858 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer