Biochemistry and Molecular Biology

2008 Recipient

Improving atomic structures at low x-ray crystallographic diffraction resolutions

Dr. Ma received the award for his work in the field of biomolecular x-ray crystallography. Structural studies of supramolecular complexes and membrane proteins are frequently hindered by large-scale anisotropic molecular deformations, which are intrinsic to biomolecular function. Capitalizing on a series of algorithmic breakthroughs in his group, Dr. Ma succeeded in devising a highly efficient normal-mode-based method for modeling anisotropic thermal parameters with an exceptionally small number of adjustable parameters. This method produces much more accurate structural models, significantly improves the fit between the structural models and the diffraction data, and reliably provides a detailed description of the dynamics, which are usually functionally important. In contrast to many structural refinement methods that are often ineffective in dealing with low-resolution structures, the normal-mode method can yield even more substantial gains in the lower-range of resolutions, which renders it applicable to a much broader spectrum of biomolecular structures. The normal-mode-based refinement method has been employed to improve the structural models of a series of biological systems, most notably potassium channel Kv1.2. The use of normal-mode-based refinement enabled visualization of nearly a third of the mass of the channel that was missing in the original structural model.

Dr. Ma's nomination was based on the following publications:

Poon BK, Chen X, Lu M, Vyas NK, Quiocho FA, Wang Q, Ma J. Normal mode refinement of anisotropic thermal parameters for a supramolecular complex at 3.42-crystallographic resolution. Proc Natl Acad Sci U S A 2007 May 8;104(19):7869-74. 

Chen X, Poon BK, Dousis A, Wang Q, Ma J. Normal-mode refinement of anisotropic thermal parameters for potassium channel KcsA at 3.2 crystallographic resolution. Structure 2007 Aug;15(8):955-62. 

Lu M, Ma JL. A minimalist network model for coarse-grained normal mode analysis and its application to biomolecular x-ray crystallography. Proc Natl Acad Sci U S A 2008 Oct 7;105(40):15358-63.