Patent EA-004002-B1 (EA)
Title: Method for predicting protein-protein interactions
Inventor: DOI HIROFUMI
IPC: G06F19/00
Filed: 2001-03-09
Abstract: 1. A method for predicting a protein or polypeptide (B) that interacts with a specific protein or polypeptide (A), wherein the method is characterized by comprising: 1) decomposing the amino acid sequence of protein or polypeptide (A) into a series of oligopeptides having a pre-determined length as sequence information; 2) searching, within a database of protein or polypeptide amino acid sequences, for a protein or polypeptide (C) comprising an amino acid sequence for each member of the series or for a protein or polypeptide (D) comprising an amino acid sequence homologous to an amino acid sequence for each member of the series; 3) carrying out local amino acid sequence alignment between said protein or polypeptide (A) and the detected protein or polypeptide (C) or detected protein or polypeptide (D); and 4) predicting whether the detected protein or polypeptide (C) and/or protein or polypeptide (D) is a protein or polypeptide (B) that interacts with the protein or polypeptide (A) based on the results of the local amino acid sequence alignment and a value calculated from a frequency of amino acids and/or a frequency of said oligopeptides in said amino acid sequence database. 2. The method according to claim 1, wherein the oligopeptide is 4-15 amino acids in length. 3. A recording medium carrying a program to predict a protein or polypeptide (B) that interacts with a specific protein or polypeptide (A), wherein the recording medium is characterized by comprising at least the following means a) SIMILAR f): a) a means for inputting amino acid sequence information of the protein or polypeptide (C) and storing the information; b) a means for decomposing said information into a series of oligopeptides having a pre-determined length as sequence information, and a means for storing the sequence information consequently obtained; c) a means for storing an input protein database; d) a means for accessing the stored protein database and detecting a protein or polypeptide (C) having an amino acid sequence of said oligopeptide or a protein or polypeptide (D) having an amino acid sequence homologous to the amino acid sequence of said oligopeptide, and a means for storing and calculating a detected result; e) a means for carrying out local alignment between said protein or polypeptide (A) and the detected protein or polypeptide (C) or protein or polypeptide (D), and a means for storing and calculating a result; and f) a means for obtaining a resultant value of a frequency of an amino acid and/or a frequency of said oligopeptide from a protein database, followed by showing an index for predicting protein-protein interactions from the resultant value and a resultant value of said local alignment, and a means for storing and displaying the result and consequently detecting protein or polypeptide (B) which interacts with the protein or polypeptide (A). 4. A recording medium characterized by comprising at least the following means in addition to the means according to claim 3: g) a means for ranking strength of protein-protein interactions among detected proteins or polypeptides (B) based on the indexes calculated from a resultant value of local alignment and a resultant value of a frequency of an amino acid and/or a frequency of an oligopeptide in a protein database in the case that more than one protein or polypeptide (B) exist that are detected, and a means for storing and displaying the result. 5. A recording medium characterized by comprising at least the following means in addition to the means according to claim 3 or 4: h) a means for displaying full-length of amino acid sequences of said protein or polypeptide (A) and said protein or polypeptide (B) that is detected, followed by indicating a location of partial sequence to be aligned in the full-length sequence in the case that amino acid partial sequences are aligned by local alignment between the protein or polypeptide (A) and the protein or polypeptide (B). 6. A recording medium characterized by comprising at least the following means in addition to the means according to claim 3, 4 or 5: i) a means for calculating a stereo structure model in the case that a stereo structure of said protein or polypeptide (A) or said protein or polypeptide (B) that is detected is known or in the case that homology modeling enables to make a stereo structure model, followed by displaying the structure of the amino acid partial sequences that are aligned by local alignment between the protein or polypeptide (A) and the protein or polypeptide (B) on the stereo structure. 7. A recording medium characterized by comprising at least the following means in addition to the means according to claim 3, 4, 5 or 6: j) a means of classifying and storing proteins in a protein database to narrow a searching area. 8. A recording medium characterized by comprising at least the following means in addition to the means according to any of preceding claims: k) a means for serially inputting each protein in a protein database as said protein or polypeptide (A). 9. A recording medium characterized by comprising at least the following means in addition to the means according to any of preceding claims: l) a means for storing a genome database. 10. A device for predicting protein-protein interactions which comprises the means that are carried by the recording medium according to claim 3, 4, 5, 6, 7, 8, or 9. 11. A method for specifying proteins or polypeptides that interact with each other, which comprises identifying a protein or polypeptide (B) that is predicted to interact with a specific protein or polypeptide (A) using the method according to claim 1 or 2, and then experimentally confirming the presence of the interaction between the protein or polypeptide (A) and the protein or polypeptide (B). 12. A method for specifying proteins or polypeptides that interact with each other, which comprises identifying a protein or polypeptide (B) that is predicted to interact with a specific protein or polypeptide (A) using the device according to claim 10, and then experimentally confirming the presence of the interaction between the protein or polypeptide (A) and the protein or polypeptide (B). 13. A protein or polypeptide that is specified by the method according to claim 11 or 12. 14. A method of screening for a compound that controls the interaction of a specific protein or polypeptide (A) with a protein or polypeptide (B), wherein the method utilizes the method according to claim 1 or 2. 15. A method of screening for a compound that controls the interaction of a specific protein or polypeptide (A) with a protein or polypeptide (B), wherein the method uses the device according to claim 10. 16. A novel compound obtained by the screening method according to claim 14 or 15. 17. A novel compound capable of controlling the interaction of a specific protein or polypeptide (A) with a protein or polypeptide (B), which is obtained by drug design based on information of a compound obtained by the screening method according to claim 14 or 15. 18. An oligopeptide comprising the amino acid sequence of SEQ ID No: 1, which is capable of controlling the interaction of verotoxin 2 (VTII) with Bcl-2. 19. An agent against cell death comprising an oligopeptide comprising the amino acid sequence of SEQ ID NO: 1. 20. An oligopeptide comprising an amino acid sequence homologous to the amino acid sequence of SEQ ID No: 1, which is capable of controlling the interaction of VTII with Bcl-2. 21. A polypeptide comprising the amino acid sequence of the oligopeptide according to claim 18 or 20, which is capable of controlling the interaction of VTII with Bcl-2. 22. A method of screening for a compound capable of controlling the interaction of VTII with Bcl-2, wherein the method utilizes the oligopeptide according to claim 18 or 20 and/or the polypeptide according to claim 21. 23. A method for determining the nucleotide sequence of an oligonucleotide coding an oligopeptide which is involved in the interaction of a specific protein or polypeptide (A) with a protein or polypeptide (B), wherein the method uses the prediction method according to claim 1 or 2 or the prediction device according to claim 10. 24. A series of combinations of human proteins that are predicted to interact with each other, obtained by the method according to claim 1 or 2 or the device according to claim 10. 25. A method for selecting a combination of proteins which interact with each other, wherein said interaction is related to a disease, wherein the method comprises selecting the combination based on the information of a known protein that can be related to the disease from the series of combinations according to claim 24. 26. A series of combinations of proteins which interact with each other, wherein said interaction is related to a disease, wherein each member of said series is selected according to the method of claim 25. 27. A method of screening for a compound which controls the interaction of a combination of proteins and/or two proteins selected from the series of combinations according to claim 26. 28. A compound obtained by the method according to claim 27. 29. A method for predicting a processing site of a protein comprising predicting the interaction of a specific protein with an enzyme cleaving said protein using the method according to claim 1 or 2 or the device according to claim 10. 30. A polypeptide comprising an amino acid sequence that is predicted to contain a protein-processing site obtained by the method according to claim 29 and/or to contain a partial sequence homologous to the processing site.