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Robust, integrated computational control of NMR experiments to achieve optimal assignment by ADAPT-NMR - PubMed

Robust, integrated computational control of NMR experiments to achieve optimal assignment by ADAPT-NMR

Arash Bahrami et al. PLoS One. 2012.

Abstract

ADAPT-NMR (Assignment-directed Data collection Algorithm utilizing a Probabilistic Toolkit in NMR) represents a groundbreaking prototype for automated protein structure determination by nuclear magnetic resonance (NMR) spectroscopy. With a [(13)C,(15)N]-labeled protein sample loaded into the NMR spectrometer, ADAPT-NMR delivers complete backbone resonance assignments and secondary structure in an optimal fashion without human intervention. ADAPT-NMR achieves this by implementing a strategy in which the goal of optimal assignment in each step determines the subsequent step by analyzing the current sum of available data. ADAPT-NMR is the first iterative and fully automated approach designed specifically for the optimal assignment of proteins with fast data collection as a byproduct of this goal. ADAPT-NMR evaluates the current spectral information, and uses a goal-directed objective function to select the optimal next data collection step(s) and then directs the NMR spectrometer to collect the selected data set. ADAPT-NMR extracts peak positions from the newly collected data and uses this information in updating the analysis resonance assignments and secondary structure. The goal-directed objective function then defines the next data collection step. The procedure continues until the collected data support comprehensive peak identification, resonance assignments at the desired level of completeness, and protein secondary structure. We present test cases in which ADAPT-NMR achieved results in two days or less that would have taken two months or more by manual approaches.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Conventional steps in protein structure determination by solution state NMR spectroscopy.
Figure 2
Figure 2. Overview of ADAPT NMR. The shaded rectangle at the left shows the sample and operations carried out by the NMR spectrometer.

Initial input is indicated in the upper left corner. The dashed line encloses components of the probabilistic network. The ADAPT-NMR output is listed at the right.

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