title: Practical model fitting approaches to the direct extraction of NMR parameters simultaneously from all dimensions of multidimensional NMR spectra.
abstract: A maximum likelihood (ML)-based approach has been established for the direct extraction of NMR parameters (e.g., frequency, amplitude, phase, and decay rate) simultaneously from all dimensions of a D-dimensional NMR spectrum. The approach, referred to here as HTFD-ML (hybrid time frequency domain maximum likelihood), constructs a time-domain model composed of a sum of exponentially-decaying sinusoidal signals. The apodized Fourier transform of this time-domain signal is a model spectrum that represents the 'best-fit' to the equivalent frequency-domain data spectrum. The desired amplitude and frequency parameters can be extracted directly from the signal model constructed by the HTFD-ML algorithm. The HTFD-ML approach presented here, as embodied in the software package CHIFIT, is designed to meet the challenges posed by model fitting of D-dimensional NMR data sets, where each consists of many data points (10(8) is not uncommon) encoding information about numerous signals (up to 10(5) for a protein of moderate size) that exhibit spectral overlap. The suitability of the approach is demonstrated by its application to the concerted analysis of a series of ten 2D 1H-15N HSQC experiments measuring 15N T1 relaxation. In addition to demonstrating the practicality of performing maximum likelihood analysis on large, multidimensional NMR spectra, the results demonstrate that this parametric model-fitting approach provides more accurate amplitude and frequency estimates than those obtained from conventional peak-based analysis of the FT spectrum. The improved performance of the model fitting approach derives from its ability to take into account the simultaneous contributions of all signals in a crowded spectral region (deconvolution) as well as to incorporate prior knowledge in constructing models to fit the data.
authors.affiliation: National Magnetic Resonance Facility at Madison, Department of Biochemistry, University of Wisconsin-Madison 53706, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Chylla
authors.forename: B F
authors.initials: BF
authors.lastname: Volkman
authors.forename: J L
authors.initials: JL
authors.lastname: Markley
mesh_terms: D000465:Algorithms; D000818:Animals; D006454:Hemoglobins / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry; D016013:Likelihood Functions; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D009587:Nitrogen Isotopes; D011077:Polychaeta / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*
chemical_list: D006454:Hemoglobins; D009587:Nitrogen Isotopes; D011506:Proteins; D006859:Hydrogen