(C) 2002, SNU Biointelligence Lab, Strategies for the development of a peptide computer Hubert Hug and Rainer Schuler Bioinformatics, vol 17 No.4 (2001) MEC Seminar Su Dong Kim

(C) 2002, SNU Biointelligence Lab, Introduction 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, 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)

(C) 2002, SNU Biointelligence Lab, Comparing the quantity of an element in two sets Affinity of antibodies B > 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, Estimating the number of an element in a set 2 n : upper bound for the number of antibodies X in G Affinity of antibodies A k > X > Y 1. The set G is added to peptides E n in the defined quantity (2 n peptides) 2. Labelled antibody Y is added 3. Detect label 4. Let k = n – 1 5. The antibody A k (2 k+1 antibodies) and peptide E k (2 k peptides) are added 6. Labelled antibody Y is added 7. Detect label if no label is detected, the number of X is at least 2 k 8. Let k = k – 1 if k > 0, continue at step (5)

(C) 2002, SNU Biointelligence Lab, Extension to NP complete problems Affinity of antibodies C > A > B 1. Let m = k 2. The antibody set G k is added 3. Antibodies B are added 4. Antibodies C are added 5. Antibodies C are removed by adding epitope C in excess 6. All remaining antibodies are covalently attached 7. Let m = m – 1, if m > 0 go to step (2) 8. Add labelled antibodies A or B 9. Fluorescence is detected

(C) 2002, SNU Biointelligence Lab, Discussion Phage display libraries Antibody array