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(C) 2002, SNU Biointelligence Lab, Abstract model With hybridization of DNA molecules only a yes or no decision (binary) is possible → can be applied to NP problems The epitopes of peptides are recognizable by more than one antibody and with a different affinity → more efficient calculations become possible Under easily achievable conditions each antibody binds reliably to its peptide (epitope) Under easily achievable conditions each antibody reliably dissociates from its peptide (epitope) If necessary, all antibodies bound to the epitopes become covalently attached to their epitopes Under neither of the conditions above does any antibody bind to another peptide (epitope)
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(C) 2002, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Strategies for the development ofStrategies for the development ofa peptide computera peptide computer
Hubert Hug and Rainer SchulerBioinformatics, vol 17 No.4 (2001) 364-368
MEC SeminarSu Dong Kim
2003. 3. 20.
(C) 2002, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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IntroductionIntroduction
DNA can be used to solve computational problems by DNA hybridization Antibodies can be similarly used for calculation by specific peptide sequence recognition Peptide computer : 20 different building blocks DNA computer : 4 different building blocks The interactions between proteins and enzymatic mechanisms are
not as clearly defined as with DNAs and they are far more complex Therefore the use of proteins for calculation is expected to reach
beyond our imaginations For example, this paper considered 3 kind of problems
(C) 2002, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Abstract modelAbstract model With hybridization of DNA molecules only a yes or no decision (binary) is possible → can be applied to NP problems The epitopes of peptides are recognizable by more than one antibody and with a different affinity → more efficient calculations become possible Under easily achievable conditions each antibody binds reliably to its peptide (epitope) Under easily achievable conditions each antibody reliably dissociates from its peptide (epitope) If necessary, all antibodies bound to the epitopes become covalently
attached to their epitopes Under neither of the conditions above does any antibody bind to another peptide (epitope)
(C) 2002, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Comparing the quantity of an element in two setsComparing the quantity of an element in two sets
Affinity of antibodiesB > A2 > X > A1
1. The element X of the first set is bound to one of the possible binding sites for X on the peptide
2. The element X of the second set is bound to the other binding sites for X on the peptide
3. A set containing labelleds element of X is used to detect any free binding site for X
Detection is by fluorescence
(C) 2002, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Estimating the number of an element in a setEstimating the number of an element in a set
2n : upper bound for the number of antibodies X in GAffinity of antibodies
Ak > X > Y1. The set G is added to peptides En in the defined quantity (2n peptides)2. Labelled antibody Y is added3. Detect label4. Let k = n – 1 5. The antibody Ak (2k+1 antibodies) and peptide Ek (2k peptides) are added6. Labelled antibody Y is added7. Detect label if no label is detected, the number of X is at least 2k 8. Let k = k – 1 if k > 0, continue at step (5)
(C) 2002, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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Extension to NP complete problemsExtension to NP complete problems
Affinity of antibodiesC > A > B
1. Let m = k2. The antibody set Gk is added3. Antibodies B are added4. Antibodies C are added5. Antibodies C are removed by
adding epitope C in excess6. All remaining antibodies are
covalently attached 7. Let m = m – 1, if m > 0 go to step (2)8. Add labelled antibodies A or B9. Fluorescence is detected
(C) 2002, SNU Biointelligence Lab, http://bi.snu.ac.kr/
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DiscussionDiscussion
Phage display libraries
Antibodyarray
