Development of pseudoenergy potentials for assessing protein 3-D-1-D compatibility and detecting weak homologies.
Recent approaches to the 3-D-1-D compatibility problem have tried to predict protein 3-D structure from sequence. One of the critical factors in this issue is the evaluation of fitness between a given 3-D structure and any sequence mounted on it. We have developed an evaluation function composed of four terms, side chain packing, hydration, hydrogen bonding and local conformation potentials, which were empirically derived from 101 proteins of known structure. The efficiency of the evaluation function was tested in two ways. In the first test, the sequence of protein A is mounted (without gaps) on the structure of protein B which is greater in size than A. For 81 proteins examined, the native structure was always detected. In the second test, a standard sequence homology search is performed against the entire database, followed by an assessment of the alignment with its proposed structure, using the empirical evaluation function. When this test was applied to the 101 proteins, our evaluation function successfully discriminated truly homologous sequence pairs from non-homologous proteins even when the sequence similarities were very weak. This approach was found to have clear advantages over conventional sequence search methods.
Nishikawa
K
K
Protein Engineering Research Institute, Osaka, Japan.
Matsuo
Y
Y
D000426:Alcohol Dehydrogenase / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D016208:Databases, Factual; D008956:Models, Chemical; D008958:Models, Molecular; D016415:Sequence Alignment / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics; D014367:Tryptophan Synthase / Q000737:chemistry
D000596:Amino Acids; D003577:Cytochrome P-450 Enzyme System; D000426:Alcohol Dehydrogenase; D014367:Tryptophan Synthase