M.M. Dalkilic, PhD Monday, September 08, 2008 Class III Indiana University, Bloomington, IN Sequence Homology 1 Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 ©

Outline New Programming and written homework Friday New Reading Posted on Website Readings [R] Chaps 5 Most Important Aspect of Bioinformatics—homology search through sequence similarity (cont’d) Some vocabulary snuck in 2 Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 ©

Computation (review) Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 © 3 Algorithm “process or rules for (esp. machine) calculations. The execution of an algorithm must not include any subjective decisions, nor must it require the use of intuition or creativity” [Brassard & Bratley]

Computation (review) Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 © 4 constant Upper bound starts Upper bound

General Technique of Dynamic Programming Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 © 5 But what if data needs to be shared or the cost of redundancy is too high? Rethink computation: Dynamic Programming or Recursive Optimization Reduce cost of sharing thereby reduce cost of recursion

General Technique of Dynamic Programming Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 © 6 “ Dynamic programming reduces the running time of a recursive function to be at most the time required to evaluate the function for all arguments less than or equal to the given argument, treating the cost of a recursive call as a constant” [Sedgewick] o Top-down DP o Bottom-Up DP

Vocabulary Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 © 7 There are about a dozen words that you will encounter when engaging in bioinformatics—or computational biology. It’s important to know what they mean. I’m not going to provide a listing of all the important words, but ones that I believe are important now. ENZYME is typically a peptide (molecule made from proteins) that enables or “catalyzes” phenomenon—this could changing one molecule to another.

Vocabulary Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 © 8 The IUBMB has developed six categories tying together nomenclature with function: EC1 oxidoreductase (moving around hydrogen) EC2 tranferase (move a functional unit) EC3 hydrolase (involves H 2 O) EC4 lysase “cleave” (or cut) without using EC1 or EC3 EC5 isomerase (change in conformation) EC6 ligase (join functional units with covalent bonds) ENZYME is typically a peptide (molecule made from proteins) that enables or “catalyzes” phenomenon—this could changing one molecule to another.

Vocabulary Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 © 9 Restriction endonuclease cleaves DNA at specific sites…

Vocabulary Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 © 10 1.Replication 2.Transcription 3.Reverse Transcription 4.Translation

Vocabulary Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 © 11 3 “letters” of DNA becomes 3 “letters” of RNA becomes 1 “letter” of protein codon Six Reading Frames

Multiple Sequence Alignment of Proteins Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 © 12 i f protein A Amino acid gap

Why Alignment of Proteins? Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 © 13 i f Conjecture: Structure imparts function and similar functions should have similar structures. Therefore, align proteins to look for regions that are “similar” in sequence, since sequence determines structure and like sequences will (likely) produce similar function.

Domains and Motifs Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 © 14 Collections of motifs that perform a function Structural motifs Functional motifs Principle is how percent identity (similarity) and homology play out—above 40% (25%) percent identity one may infer a homology is plausible.

Domains and Motifs Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 © 15 Primary structure (sequence itself) Secondary structure [most common] (alpha-helix, beta- sheet) Tertiary structure is collection of secondary structure interlaced with loops Quarternary structure is combination of tertiary structures

Recurrence of Aligning two Sequences Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 © 16 # elementary particles in universe

Better Recurrences Sequence Similiarty (Computation) M.M. Dalkilic, PhD SoI Indiana University, Bloomington, IN 2008 © 17 [Waterman]