Download presentation

Presentation is loading. Please wait.

Published byMary Willis Modified over 2 years ago

1
Part I: Paper d: Protein Folding Erik Demaine, MIT Stefan Langerman, U. Bruxelles Joseph ORourke, Smith College

2
Outline zInterlocked Chains zFixed-angle chains zProducible chains zFlattenable zProof Outline zConsequence?

3
Definitions zOpen vs. closed chains. (Closed chains are more constrained.) zFlexible chains: no constraints on joint motion (each joint universal). zRigid chains: each joint is frozen, and the entire chain is rigid. zFixed-angle chains: maintain angle between links incident to each joint.

4
Crosstable of results

5
Rigid 2-chains cannot interlock

6
Flexible 2-chain can interlock with rigid 5-chain

7
Open Problem What is the smallest value of k that permits a flexible 2-chain to interlock with a flexible k-chain? Theorem shows that a rigid 5-chain suffices; presumably k > 5 is needed for a flexible chain.

8
Demaine, Langermann, JOR: Main Theorem Theorem 1: A fixed angle polygonal ( )-chain is -producible ( 90 º ), if and only if it is flattenable.

9
Consequence Theorem 2: The -producible configurations of chains are rare: The probability that a random configuration of a random chain is -producible approaches 0 as n.

10
Chymotrypsin: unfolded & folded

11
Protein Folding

12
Main Theorem Theorem 1: A fixed angle polygonal ( )-chain is -producible ( 90 º ), if and only if it is flattenable.

13
Fixed-angle chain

14
( )-chain

15
Locked 3D Chains [Cantarella & Johnston 1998; Biedl, Demaine, Demaine, Lazard, Lubiw, ORourke, Overmars, Robbins, Streinu, Toussaint, Whitesides 1999] Cannot straighten some chains, even with universal joints.

16
Ribosome The majority of the surface of the tunnel is trained by field I (yellow) and V (red) of 23S and by the nonglobular areas of the proteins L4, L22 and L39e. Incipient polypeptide first meets field V then field II and IV with the proteins L4 and L22. Half of the tunnel is constituted by field I and III and the L39e protein.

17
Ribosome (closeup) The 2 proteins, L22 and L4 (in dark blue) form what appears to be an open door. This crossing point could be the place where the nature of incipient polypeptide is detected and from which information would be transmitted to the surface of ribosome, perhaps through proteins L22 and L4.

18
Constraint: Cone

19
Main Theorem Theorem 1: A fixed angle polygonal ( )-chain is -producible ( 90 º ), if and only if it is flattenable.

20
-production -production

21
Lemma 1 An ( )-chain can be produced only in a cone with (whole) apex angle of.

22
B: Emergence cone

23
-chain -chain

24
Canonical Configuration Lemma 2. If a configuration of a chain is - producible, then it can be moved inside the cone to a canonical coiled configuration, the -CCC.

25
-CCC -CCC

26
Proof figure

27
Proof Idea zReplay production movements in time reversal, coiling the chain inside the cone.

28
Main Theorem Theorem 1: A fixed angle polygonal ( )-chain is -producible ( 90 º ), if and only if it is flattenable.

29
Flattenable A configuration of a chain if flattenable if it can be reconfigured, without self- intersection, so that it lies flat in a plane. Otherwise the configuration is unflattenable, or locked.

30
Every 90 º -angle chain has a flattenable configuration.

31
Unflattenable chain

32
Main Theorem (revisited) Theorem 1: All -producible ( )-chains are flattenable, provided 90 º. All flat configurations of ( )-chains are - producible, for 90 º.

33
Logical Flow of Ideas z -producible -CCC canonical configuration flattened -CCC z -producible flattenable flattenable not locked locked abundant not locked rare rare search easier?

34
Consequence (revisited) Theorem 2: The -producible configurations of chains are rare: The probability that a random configuration of a random chain is -producible approaches 0 as n.

35
Configuration Space All configurations Flattenable configurations

36
Why restriction to 90 º ?

37
Protein Sidechains

38
Tunnel Exit Localization of proteins at the exit of the tunnel.

39
Open Problems: Locked Equilateral Chains? (1)Is there a configuration of a chain with universal joints, all of whose links have the same length, that is locked? (2)Is there a configuration of a 90 o fixed- angle chain, all of whose links have the same length, that is locked? Perhaps: No? Perhaps: Yes for 1+ ?

40
Ribosome structure The figure at bottom represents the interactions allowing pairing codon- anticodon. The elements of contact are marked (A) with (c). The anticodon of ARNt is in dark blue and the codon of ARNm in the site P is in red.

Similar presentations

© 2016 SlidePlayer.com Inc.

All rights reserved.

Ads by Google