Biochemical Reactions
description
Transcript of Biochemical Reactions
BiochemicalReactions
computationinputs outputs
Molecular Triggers
Molecular Products
Synthesizing Biological ComputationSynthesizing Biological Computation
Protein-Protein Chemistry at the Cellular Level
Design a system that computes output quantitiesas functions of input quantities.
Synthesizing Biological ComputationSynthesizing Biological Computation
BiochemicalReactions
given obtain
Quantities of Different
Types
Quantities of Different
Types
Design a system that computes output quantitiesas functions of input quantities.
Synthesizing Biological ComputationSynthesizing Biological Computation
BiochemicalReactions
independentfor us to design
specified
Z=X×Y
X
Y
Z
Logic Gates: how digital values are computed.
Biochemical Reactions: how types of molecules combine.
“XOR” gate
0011
0101
0110
1x 2x g
Basic Mechanisms
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1x
2x
g
+2a b c
Biochemical Reactions
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cellspecies count
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Discrete chemical kinetics; spatial homogeneity.
Biochemical Reactions
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slow
medium
fast
Relative rates or (reaction propensities):
Discrete chemical kinetics; spatial homogeneity.
Design a system that computes output quantitiesas functions of input quantities.
Synthesizing Biological Computation
BiochemicalReactions
given obtain
Quantities of Different
Types
Quantities of Different
TypesM NM2
independent
for us to design
specified
Example: MultiplicationExample: Multiplication
Use working types a, y′.
slow ax
med.yy′
fasta
v. fastzy′ya a
obtain of zYX
Produce of type z.YXStart with of type x. X Start with of type y. Y
Iterate!
Start with no amount of types b and c.
Example: ExponentiationStart with M of type m. Produce of type n.
M2Use working types a, b, c.
Start with any non-zero amount of types a and n.
nana fast2meda
obtain 1 of n
bmslow
cbnb 2v. fast
fastb
ncmed.
obtain of n M2
Functional Dependencies
Logarithm
Linear
Raising-to-a-Power
2MN 2MN Exponentiation
)(log2 MN )(log2 MN
MN MN
PMN PMN
The probability that a given reaction is the next to fire is proportional to:
• Its rate.• The quantities of its reactants.
See D. Gillespie, “Stochastic Chemical Kinetics”, 2006.
Stochastic Kinetics
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k1
k2
k3
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Modular SynthesisModular Synthesis
Deterministic Deterministic ModuleModule
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Stochastic Stochastic ModuleModule
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initializing, reinforcing,stabilizing,purifying, and working reactions
linear, exponentiation, logarithm,raising-to-a-power, etc.
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Modular SynthesisModular Synthesis
StochasticModule
DeterministicModule
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Compose modules to achieved desired probabilistic response.
Composition requires “regulatory gluing”.
02MN 02MN
)(log 02 NP )(log 02 NP
00
PNQ 00
PNQ
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• Structure computation to obtain initial choice probabilistically.
• Then amplify this choice and inhibit other choices.
Method is:
• Precise.• Robust.• Programmable.
Strategy:
With “locking”, produces designs that are independent of rates.
Modular SynthesisModular Synthesis
CAD Tool
• Library of biochemical models.
• Designated input and output types.
• Specific quantities (or ranges) of input types.
• Target functional dependencies.
• Target probability distribution.
Brian’s Automated Modular Biochemical Instantiator (BAMBI)
Given:
Outputs:• Reactions/parameters implementing specification.• Detailed measures of accuracy and robustness.
Targets can be nearly any analytic function or data set.
Computational Infrastructure• Implementing a “front-end” database of biochemical models in
Structured Query Language (SQL) from online repositories: BioBricks, SBML.org, …
• Implementing “back-end” number crunching algorithms for analysis and synthesis on a farm of high-performance processors.
IBM System Z MainframeFarm of Cell B.E.
processors (from Sony Playstations 3’s)