Abstract
The transmission of genomic information from coding sequence to protein structure during protein synthesis is subject to stochastic errors. To analyze transmission limits in the presence of spurious errors, Shannon's noisy channel theorem is applied to a communication channel between amino acid sequences and their structures established from a large-scale statistical analysis of protein atomic coordinates. While Shannon's theorem confirms that in close to native conformations information is transmitted with limited error probability, additional random errors in sequence (amino acid substitutions) and in structure (structural defects) trigger a decrease in communication capacity toward a Shannon limit at 0.010 bits per amino acid symbol at which communication breaks down. In several controls, simulated error rates above a critical threshold and models of unfolded structures always produce capacities below this limiting value. Thus an essential biological system can be realistically modeled as a digital communication channel that is (a) sensitive to random errors and (b) restricted by a Shannon error limit. This forms a novel basis for predictions consistent with observed rates of defective ribosomal products during protein synthesis, and with the estimated excess of mutual information in protein contact potentials.
Highlights
In the sixty years since its formulation communication theory [1] has shaped modern technology, from integrated circuits to satellite communication
Yockey, who pioneered an information theory approach to the Central Dogma [6], applied the Shannon-Weaver communication model [1] to describe the flow of information from DNA to the amino acid sequence but did not provide a detailed information theoretic description of the folded state
Model formulation: Shannon-Weaver communication between protein sequences and structures Cellular production of polypeptides was modeled as a serial process where over time many chains are synthesized by the translational and ribosomal apparatus
Summary
In the sixty years since its formulation communication theory [1] has shaped modern technology, from integrated circuits to satellite communication. The generality of Shannon’s results suggests that biological systems may use Shannon codes, such as in the transfer of genomic information during cellular protein synthesis. 4 bits per residue cannot be the true rate of information transfer between sequence and structure. This follows from (a) Anfinsen’s result that a fully translated amino acid sequence is necessary and sufficient for a protein to fold into its native state [9], and from (b) Levinthal’s argument that folding cannot be realistically achieved by sampling an astronomical number of configurations [10]. For information transmission between sequence and structure to be realistic, transmission rate must be much smaller than ,4 bits per residue
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