Prediction of parathyroid hormone signalling potency using SVMs.
Parathyroid hormone is the most important endocrine regulator of calcium concentration. Its N-terminal fragment (1-34) has sufficient activity for biological function. Recently, site-directed mutagenesis studies demonstrated that substitutions at several positions within shorter analogues (1-14) can enhance the bioactivity to greater than that of PTH (1-34). However, designing the optimal sequence combination is not simple due to complex combinatorial problems. In this study, support vector machines were introduced to predict the biological activity of modified PTH (1-14) analogues using mono-substituted experimental data and to analyze the key physicochemical properties at each position that correlated with bioactivity. This systematic approach can reduce the time and effort needed to obtain desirable molecules by bench experiments and provide useful information in the design of simpler activating molecules.
Yoo
Ahrim
A
Department of Chemical and Biological Engineering, Korea University, Seoul 136-713, Korea.
Ko
Sunggeon
S
Lim
Sung-Kil
SK
Lee
Weontae
W
Yang
Dae Ryook
DR
D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002627:Chemistry, Physical; D019295:Computational Biology; D003198:Computer Simulation; D000242:Cyclic AMP / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004703:Endocrine System; D005818:Genetic Engineering; D005822:Genetic Vectors; D006801:Humans; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D019379:Teriparatide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D015533:Transcriptional Activation
D050505:Mutant Proteins; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D000242:Cyclic AMP; C035748:parathyroid hormone (1-34)amide; D002118:Calcium