Sequence specific resonance assignment via Multicanonical Monte Carlo search using an ABACUS approach
- 113 Downloads
ABACUS [Grishaev et al. (2005) Proteins 61:36–43] is a novel protocol for automated protein structure determination via NMR. ABACUS starts from molecular fragments defined by unassigned J-coupled spin-systems and involves a Monte Carlo stochastic search in assignment space, probabilistic sequence selection, and assembly of fragments into structures that are used to guide the stochastic search. Here, we report further development of the two main algorithms that increase the flexibility and robustness of the method. Performance of the BACUS [Grishaev and Llinás (2004) J Biomol NMR 28:1–101] algorithm was significantly improved through use of sequential connectivities available from through-bond correlated 3D-NMR experiments, and a new set of likelihood probabilities derived from a database of 56 ultra high resolution X-ray structures. A Multicanonical Monte Carlo procedure, Fragment Monte Carlo (FMC), was developed for sequence-specific assignment of spin-systems. It relies on an enhanced assignment sampling and provides the uncertainty of assignments in a quantitative manner. The efficiency of the protocol was validated on data from four proteins of between 68–116 residues, yielding 100% accuracy in sequence specific assignment of backbone and side chain resonances.
KeywordsBACUS NOE identification Fragment Monte Carlo Resonance assignment
- Goddard TD, Kneller DG (2003) Sparky - NMR assignment and integration software. University of California, San FranciscoGoogle Scholar
- Güntert P (2004) Automated NMR structure calculation with CYANA. Methods Mol Biol 278:353–378Google Scholar
- Yee A, Chang X, Pineda-Lucena A, Wu B, Semesi A, Le B, Ramelot T, Lee GM, Bhattacharyya S, Gutierrez A, Denisov A, Lee C, Cort JR, Kozlov G, Liao J, Finak G, Chen L, Wishart D, Lee W, McIntosh LP, Gehring K, Kennedy MA, Edwards AM, Arrowsmith CH (2002) An NMR approach to structural proteomics. Proc Nat Acad Sci USA 99:1825–1830CrossRefADSGoogle Scholar