Development of a four-body statistical pseudo-potential to discriminate native from non-native protein conformations.
BACKGROUND
Most scoring functions used in protein fold recognition employ two-body (pseudo) potential energies. The use of higher-order terms may improve the performance of current algorithms.


METHODS
Proteins are represented by the side chain centroids of amino acids. Delaunay tessellation of this representation defines all sets of nearest neighbor quadruplets of amino acids. Four-body contact scoring function (log likelihoods of residue quadruplet compositions) is derived by the analysis of a diverse set of proteins with known structures. A test protein is characterized by the total score calculated as the sum of the individual log likelihoods of composing amino acid quadruplets.


RESULTS
The scoring function distinguishes native from partially unfolded or deliberately misfolded structures. It also discriminates between pre- and post-transition state and native structures in the folding simulations trajectory of Chymotrypsin Inhibitor 2 (CI2).
Krishnamoorthy
Bala
B
Department of Operations Research, CB 3180, UNC Chapel Hill, NC 27599, USA.
Tropsha
Alexander
A
D000465:Algorithms; D000595:Amino Acid Sequence; D003461:Crystallography / Q000379:methods*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D020539:Sequence Analysis, Protein / Q000379:methods*
D011506:Proteins