AndMotioninBiology

4..TheLeventhalParadox

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Given a small protein consisting of about one hundred amino acids, assume that thereare three conformations per peptide bond. This gives us 3¹⁰⁰= 5 10⁴⁷conformations.If it takes 10⁻¹⁵seconds to sample each conformation, sampling all the conformationswouldtake510³²seconds.Thisisequivalentto1.610²⁵years!Buteachproteinfoldsquicklyintoasinglestablenativeconformation.Howdoesthishappen?

1. 4.1.Energyand Kinematics

Proteins can fold quickly into a stable conformation because energy and kinematics de-terminethemajorconfiguration.Ingeneral,theproteinwillfoldtoitsminimumenergy

configuration.This is not always the case, however, because the minimum energy con-figuration may not be as quickly/easily reached as a particular higher-energy yet stillfunctional configuration. Kinematics must therefore be taken into consideration. Ratherthanhavecomplexknots,aproteinwillhaveasimpletopology.

5. 5.StructuralMotifRecognition

Givenanaminoacidresiduesequence,doesitfoldasacoiledcoil, betabarrel, betahelix,zinc finger, or other structural motif? The basic steps involved in recognizing structuralmotifsare:

1. 
   Collectadatabaseofknownmotifsandcorrespondingaminoacidsubsequences.
   
2. 
   Deviseamethod/modelto”match”anewsequencetotheexistingmotifdatabase.
   
3. 
   Verifycomputationallyonatestset.
   
4. 
   Verifyinlab.
   

Possiblemethodsformatchingasequencetothemotifdatabaseinclude:

• 
  Alignment
  
• 
  Neuralnets
  
• 
  HiddenMarkovModels
  
• 
  Threading
  
• 
  Profile-basedmethods
  
• 
  Otherstatisticalmethods
  

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