ahiddenmarkovmodelforproteinsecondarystructureprediction.pptVIP

A Hidden Markov Model for Protein Secondary Structure Prediction Wei-Mou Zheng Institute of Theoretical Physics Academia Sinica PO Box 2735, Beijing 100080 zheng@itp.ac.cn Outline Protein structure A brief review of secondary structure prediction Hidden Markov model: simple-minded Hidden Markov model: realistic Discussion References Discussions HMM using refined conformational states and window scores is efficient for protein secondary structure prediction. Better score system should cover more correlation between conformation and sequence. Combining homologous information will improve the prediction accuracy. From secondary structure to 3D structure (structure codes: discretized 3D conformational states) * Protein sequences are written in 20 letters (20 Naturally-occurring amino acid residues): AVCDE FGHIW KLMNY PQRST Hydrophobic Charged+- Polar Cis- Trans- Residues form a directed chain Rasmol ribbon diagram of GB1 Helix (pink), sheets (yellow) and coil (grey) Hydrogen-bond network 3D structure → secondary structure written in three letters:H, E, C. H: E: C = 34.9: 21.8: 43.3 Bayes formula Count of Generally, P(x, y) = P(x|y)P(y), Protein sequence A, {ai}, i=1,2,…,n Secondary structure sequence S, {si}, i=1,2,…,n Secendary structure prediction: 1D amino acid sequences → 1D secondary structure sequence An old problem for more than 30 years Inference of S from A: P(S |A ) 1. Simple Chou-fasman approach Chou-Fasman’s propensity of amino acid to conformational state + independence approximation Parameter Training Propensities q(a,s) Counts (20x3) from a database: N(a, s) sum over a → N(s), sum over s → N(a), sum over a and s → N