>>Published online before print January 29, 2002, 10.1073/pnas.032522499;
Proc. Natl. Acad. Sci. USA, Vol. 99, Issue 3, 1274-1279, February 5, 2002
Biophysics
Flexibility and packing in proteins
Bertil Halle*
Department of Biophysical Chemistry, Lund University, Box 124, SE-22100 Lund, Sweden
Edited by Alan Fersht, University of Cambridge, Cambridge, United Kingdom, and approved December 4, 2001 (received for review October 2, 2001)
Structural flexibility is an essential attribute, without which few proteins could carry out their biological functions. Much information about protein flexibility has come from x-ray crystallography, in the form of atomic mean-square displacements (AMSDs) or B factors. Profiles showing the AMSD variation along the polypeptide chain are usually interpreted in dynamical terms but are ultimately governed by the local features of a highly complex energy landscape. Here, we bypass this complexity by showing that the AMSD profile is essentially determined by spatial variations in local packing density. On the basis of elementary statistical mechanics and generic features of atomic distributions in proteins, we predict a direct inverse proportionality between the AMSD and the contact density, i.e., the number of noncovalent neighbor atoms within a local region of ~1.5 nm3 volume. Testing this local density model against a set of high-quality crystal structures of 38 nonhomologous proteins, we find that it accurately and consistently reproduces the prominent peaks in the AMSD profile and even captures minor features, such as the periodic AMSD variation within helices. The predicted rigidifying effect of crystal contacts also agrees with experimental data. With regard to accuracy and computational efficiency, the model is clearly superior to its predecessors. The quantitative link between flexibility and packing density found here implies that AMSDs provide little independent information beyond that contained in the mean atomic coordinates.<<
Makes me wonder how well current X-Ray crystallography companies will do with their deals. It appears the technique is in need of further refinement to produce meaningful results, and that may explain why nobody is paying really big bucks for it yet. BWDIK.
Cheers, Tuck |
