Development of a four-body statistical pseudo-potential to discriminate native from non-native protein conformations

• Published in: Bioinformatics 2003-08, Vol.19 (12), p.1540-1548
• Main Authors: Krishnamoorthy, Bala, Tropsha, Alexander
• Format: Article
• Language: English
• Subjects: Algorithms; Amino Acid Sequence; Biological and medical sciences; Crystallography - methods; Fundamental and applied biological sciences. Psychology; General aspects; Mathematics in biology. Statistical analysis. Models. Metrology. Data processing in biology (general aspects); Models, Molecular; Molecular Sequence Data; Protein Conformation; Protein Folding; Proteins - chemistry; Quantitative Structure-Activity Relationship; Sequence Analysis, Protein - methods
• ISSN: 1367-4803; 1460-2059; 1367-4811
• DOI: 10.1093/bioinformatics/btg186

Motivation: 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). Availability: All codes are written in C/C++. Programs are available from the authors on request.. Contact: [e-mail] * To whom correspondence should be addressed.