Structure fluctuations and conformational changes in protein binding.
Structure fluctuations and conformational changes accompany all biological processes involving macromolecules. The paper presents a classification of protein residues based on the normalized equilibrium fluctuations of the residue centers of mass in proteins and a statistical analysis of conformation changes in the side-chains upon binding. Normal mode analysis and an elastic network model were applied to a set of protein complexes to calculate the residue fluctuations and develop the residue classification. Comparison with a classification based on normalized B-factors suggests that the B-factors may underestimate protein flexibility in solvent. Our classification shows that protein loops and disordered fragments are enriched with highly fluctuating residues and depleted with weakly fluctuating residues. Strategies for engineering thermostable proteins are discussed. To calculate the dihedral angles distribution functions, the configuration space was divided into cells by a cubic grid. The effect of protein association on the distribution functions depends on the amino acid type and a grid step in the dihedral angles space. The changes in the dihedral angles increase from the near-backbone dihedral angle to the most distant one, for most residues. On average, one fifth of the interface residues change the rotamer state upon binding, whereas the rest of the interface residues undergo local readjustments within the same rotamer.
Center for Bioinformatics, University of Kansas, Lawrence, KS 66047, USA. ruvinsky@ku.edu
Anatoly M
AM
Ruvinsky
Tatsiana
T
Kirys
Alexander V
AV
Tuzikov
Ilya A
IA
Vakser
D001665:Binding Sites; D030562:Databases, Protein; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
D011506:Proteins