Exhaustive enumeration of protein conformations using experimental restraints.
We present an efficient new algorithm that enumerates all possible conformations of a protein that satisfy a given set of distance restraints. Rapid growth of all possible self-avoiding conformations on the diamond lattice provides construction of alpha-carbon representations of a protein fold. We investigated the dependence of the number of conformations on pairwise distance restraints for the proteins crambin, pancreatic trypsin inhibitor, and ubiquitin. Knowledge of between one and two contacts per monomer is shown to be sufficient to restrict the number of candidate structures to approximately 1,000 conformations. Pairwise RMS deviations of atomic position comparisons between pairs of these 1,000 structures revealed that these conformations can be grouped into about 25 families of structures. These results suggest a new approach to assessing alternative protein folds given a very limited number of distance restraints. Such restraints are available from several experimental techniques such as NMR, NOESY, energy transfer fluorescence spectroscopy, and crosslinking experiments. This work focuses on exhaustive enumeration of protein structures with emphasis on the possible use of NOESY-determined distance restraints.
DeWitte
R S
RS
Department of Chemistry, Harvard University, Cambridge Massachusetts 02138, USA.
Michnick
S W
SW
Shakhnovich
E I
EI
D000465:Algorithms; D007611:Aprotinin / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010940:Plant Proteins / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D014452:Ubiquitins / Q000737:chemistry
D010940:Plant Proteins; D014452:Ubiquitins; C024934:crambin protein, Crambe abyssinica; D007611:Aprotinin