AHiddenMarkovModelforProteinSecondaryStructure.pptVIP

A Hidden Markov Model for Protein Secondary Structure Prediction;Outline;;Cis-;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 q(a,s) = [N(a,s) N] / [N(a) N(s)].;;Hidden Markov Model (HMM): simple-minded Bayesian formula: P(S|A) = P(S,A)/P(A) ~ P(S,A) = P(A|S) P(S) Simple version emitting ai at si Markov chain according to P(a|s) For hidden sequence Forward and backward functions;Initial conditions and recursion relations Partition function Linear algorithm: Dynamic programming Baum-Welch (sum) Viterbi (max); Prob(si=s, si+1=s’) = Ai(s) tss’ P(ai+1|s’) Bi+1(s’)/Z Prob(si:j) ;Hidden Markov Model: Realistic 1) Strong correlation in conformational states: at least two consicutive E and three consicutive H refined conformational states (243 → 75) 2) Emission probabilities → improved window scores Proportion of accurately predicted sites ~ 70% (compared with 65% for prediction based on a single sequence) No post-prediction filtering Integrated (overall) estimation of refined conformation states Measure of prediction