Weighting of Experimental Evidence in Macromolecular Structure Determination

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 6; pp. 1756 - 1761
• Main Authors: Habeck, Michael, Rieping, Wolfgang, Nilges, Michael
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 07-02-2006; National Acad Sciences
• Subjects: Bias; Biological Sciences; Biophysical Phenomena; Biophysics; Coordinate systems; Error rates; Experimental data; Force field; Histograms; Logarithms; Macromolecular Substances - chemistry; Magnetic Resonance Spectroscopy; Mathematical functions; Molecular Structure; Molecular Weight; Probability theory; Reproducibility of Results; Statistical analysis; Term weighting
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0506412103

The determination of macromolecular structures requires weighting of experimental evidence relative to prior physical information. Although it can critically affect the quality of the calculated structures, experimental data are routinely weighted on an empirical basis. At present, cross-validation is the most rigorous method to determine the best weight. We describe a general method to adaptively weight experimental data in the course of structure calculation. It is further shown that the necessity to define weights for the data can be completely alleviated. We demonstrate the method on a structure calculation from NMR data and find that the resulting structures are optimal in terms of accuracy and structural quality. Our method is devoid of the bias imposed by an empirical choice of the weight and has some advantages over estimating the weight by cross-validation.