PEDS Advance Access originally published online on April 21, 2005
Protein Engineering Design and Selection 2005 18(5):209-219; doi:10.1093/protein/gzi026
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Fold recognition aided by constraints from small angle X-ray scattering data
1Departments of Physics and Applied Physics and Laboratory for Advanced Materials, Stanford University, CA 94305 and 2Laboratory of Computational Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
3 To whom correspondence should be addressed. E-mail: zhengwj{at}helix.nih.gov
We performed a systematic exploration of the use of structural information derived from small angle X-ray scattering (SAXS) measurements to improve fold recognition. SAXS data provide the Fourier transform of the histogram of atomic pair distances (pair distribution function) for a given protein and hence can serve as a structural constraint on methods used to determine the native conformational fold of the protein. Here we used it to construct a similarity-based fitness score with which to evaluate candidate structures generated by a threading procedure. In order to combine the SAXS scores with the standard energy scores and other 1D profile-based scores used in threading, we made use both of a linear regression method and of a neural network-based technique to obtain optimal combined fitness scores and applied them to the ranking of candidate structures. Our results show that the use of SAXS data with gapless threading significantly improves the performance of fold recognition.
Keywords: fold recognition/linear regression/neural network/small angle X-ray scattering
Received November 10, 2004; revised March 7, 2005; accepted March 25, 2005.
Edited by Fred Cohen