Coding Theory and Protein SynthesisAgenda It is the glory of God to conceal a matter; to search out a matter is the glory of kings. Proverbs 25:2 (NIV)Nucleotides: Did nature select a parity check code?Protein: Degeneracy of the genetic codeProtein: Information theory and binding sitesPowerPoint PresentationSlide 7Evidence: Is there evidence of error control in protein synthesis process?Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Construction and control: Quantify and Optimize Protein TranslationSlide 21AcknowledgmentsCoding Theory and Protein Coding Theory and Protein SynthesisSynthesisAvogadro-Scale Engineering: Form and FunctionAvogadro-Scale Engineering: Form and FunctionNovember 18, 19 2003November 18, 19 2003Elebeoba E. MayElebeoba E. MayComputational Biology DepartmentComputational Biology DepartmentSandia National LaboratoriesSandia National Laboratories*[email protected]*[email protected] is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company,for the United States Department of Energy under contract DE-AC04-94AL85000.AgendaAgenda It is the glory of God to conceal a matter; to search out a matter is the glory of kings. Proverbs 25:2 (NIV)•Error Control at Diverse Molecular Scales•Coding Theory Models of Protein Synthesis–Gatlin–Yockey–May et al.•Applications of Coding Theory to–Genetic Classification–Molecular Computation–Construction and Control in Protein SynthesisNucleotides: Did nature select a parity check code?D. A. Mac Dónaill : “ Numerical Interpretation of nucleotides depicted as positions on a B^4 hypercube: (a) even-parity nucleotides; (b) odd-parity nucleotides. The natural alphabet is structured as an error-checking code.” *D.A. Mac Dónaill, “A parity code interpretation of nucleotide alphabet composition,” Chem. Comm. (2002) 2062-2063 and http://www.tcd.ie/Chemistry/People/macdonaill/Protein: Degeneracy of the genetic codeB. Hayes : “how quickly a biochemical puzzle … was reduced to an abstract problem in symbol manipulation.” B. Hayes, “The Invention of the Genetic Code,” Sc. Am. 1998 (Physicist George Gamow and coding-theorist Solomon W. Golomb. Experimental evidence from Marshall W. Nirenberg and J. Heinrich Matthaei, NIH)http://www.people.virginia.edu/~rjh9u/code.htmlProtein: Information theory and binding sitesT. D. Schneider : “Strong minor groove base conservation in sequence logos implies DNA distortion or base flipping during replication and transcription initiation,” Nucleic Acids Research, 2001, Vol. 29, No. 23 4881-4891Comparison of microbial genome base mutation rate to genome size: exhibits power law behavior; inverse relation between genome size and base mutation rate.Mutation RatesMutation Rates• RNA viruses: 1 - 0.1• DNA microbes: 1/300• Higher eukaryotes: 1/300 EfGn Genome: Increased length, increased fidelityComparison of higher eukaryotic genome base mutation rate to genome size: inverse relation between genome size and base mutation rate.G. Battail: “… increasing the codeword length results in a decreasing probability of error…”Evidence: Is there evidence of error control in protein synthesis process?Liebovitch et al. 1996, Rosen and Moore 2003 computational experiments did not find evidence for linear block codesApproach not comprehensive, did not consider convolutional coding or noiseMay et al. Looked for optimal generator for translation initiation sitesHighly probable for encoding model not to conform to known error control codes.AgendaAgenda It is the glory of God to conceal a matter; to search out a matter is the glory of kings. Proverbs 25:2 (NIV)•Error Control at Diverse Molecular Scales•Coding Theory Models of Protein Synthesis–Gatlin–Yockey–May et al.•Applications of Coding Theory to–Genetic Classification–Molecular Computation–Construction and Control in Protein Synthesis(eukaryotes)Central Dogma of Genetics = Genetic Information Central Dogma of Genetics = Genetic Information TransmissionTransmission(http://www-stat.stanford.edu/~susan/courses/s166/central.gif)EncodeChannelBDecodeACoding Theory Models of Protein Synthesis Gatlin, LL., Information theory and the Living System. 1972.Yockey, Hubert, Information Theory and Molecular Biology. 1992Genetic EncoderCoding Theory View of Protein Synthesis, May et al., JFI 2004Genetic InformationErrorsGenetic Channel3’AUG UAAmRNAGenetic DecoderPrincipal Hypothesis:Principal Hypothesis: If mRNA is viewed If mRNA is viewed as a noisy encoded signal, it is feasible to use as a noisy encoded signal, it is feasible to use principles of error control coding theory to principles of error control coding theory to interpret the genetic translation initiation interpret the genetic translation initiation mechanismmechanism111-000-000-111111-000-000-111111-001-000-1101-0-0-1k-bitInformationErrors!111-001-000-110n-bitInformationNoise+n-bitInformationAB~ k-bitInformationChannelEncoderDecoder1-0-0-11-0-0-1Engineering Communication System Error Control111-000-000-111111-000-000-111111-001-000-1101-0-0-1k-bitInformationErrors!111-001-000-110n-bitInformationNoise+n-bitInformationAB~ k-bitInformationChannelEncoderDecoder1-0-0-11-0-0-1Engineering Communication System Error Control????????AgendaAgenda It is the glory of God to conceal a matter; to search out a matter is the glory of kings. Proverbs 25:2 (NIV)•Error Control at Diverse Molecular Scales•Coding Theory Models of Protein Synthesis–Gatlin–Yockey–May et al.•Applications of Coding Theory to–Genetic Classification–Molecular Computation–Construction and Control in Protein Synthesis•Efficient Coding for the Desoxyribonucleic Channel (S. W. Golomb 1962)–Applied Biorthogonal codes to genetic coding problem (the codon to amino acid mapping challenge)•Andrzej K. Konopka (1984)•Gerard Battail •Table-Based Convolutional Code for E. coli Promoter (P. Bermel) –Based on the informational content of E. coli promoter, approximates the coding rate for promoter region as 1/9.–Developed a possible 1/5 binary code for E. coli promoter region.Biological Coding TheoryBiological Coding Theory David Loewenstern, et. al•Compression for DNA sequence classification Leonard Adleman, et al.; Lila Kari, et al.•Molecular computation•Encoding for DNA computing•Error-control codingThomas Schneider, et al.•Biological