Abstract
BackgroundAll the information necessary for protein folding is supposed to be present in the amino acid sequence. It is still not possible to provide specific ab initio structure predictions by bioinformatical methods. It is suspected that additional folding information is present in protein coding nucleic acid sequences, but this is not represented by the known genetic code.ResultsNucleic acid subsequences comprising the 1st and/or 3rd codon residues in mRNAs express significantly higher free folding energy (FFE) than the subsequence containing only the 2nd residues (p < 0.0001, n = 81). This periodic FFE difference is not present in introns. It is therefore a specific physico-chemical characteristic of coding sequences and might contribute to unambiguous definition of codon boundaries during translation. The FFEs of the 1st and 3rd residues are additive, which suggests that these residues contain a significant number of complementary bases and that may contribute to selection for local RNA secondary structures in coding regions. This periodic, codon-related structure-formation of mRNAs indicates a connection between the structures of exons and the corresponding (translated) proteins. The folding energy dot plots of RNAs and the residue contact maps of the coded proteins are indeed similar. Residue contact statistics using 81 different protein structures confirmed that amino acids that are coded by partially reverse and complementary codons (Watson-Crick (WC) base pairs at the 1st and 3rd codon positions and translated in reverse orientation) are preferentially co-located in protein structures.ConclusionExons are distinguished from introns, and codon boundaries are physico-chemically defined, by periodically distributed FFE differences between codon positions. There is a selection for local RNA secondary structures in coding regions and this nucleic acid structure resembles the folding profiles of the coded proteins. The preferentially (specifically) interacting amino acids are coded by partially complementary codons, which strongly supports the connection between mRNA and the corresponding protein structures and indicates that there is protein folding information in nucleic acids that is not present in the genetic code. This might suggest an additional explanation of codon redundancy.
Highlights
All the information necessary for protein folding is supposed to be present in the amino acid sequence
It is widely believed that the amino acid sequence contains all the information necessary to make up the correct threedimensional structure, since protein folding is apparently thermodynamically determined; i.e., given a proper environment, a protein will fold up spontaneously
The free folding energy is defined as FFE =/L × 100, where L is the length of the nucleic acid, i.e., free energy difference between native and shuffled nucleic acids per 100 nucleotides
Summary
All the information necessary for protein folding is supposed to be present in the amino acid sequence. It is widely believed that the amino acid sequence contains all the information necessary to make up the correct threedimensional structure, since protein folding is apparently thermodynamically determined; i.e., given a proper environment, a protein will fold up spontaneously. This is called Anfinsen's thermodynamic principle [1]. Another observation concerning the code redundancy dilemma is that there is a widespread selection (preference) for local RNA secondary structure in protein coding regions [13]. The immediate question is whether there is some logical connection between the possible optimal RNA structures and the possible optimal biologically active protein structures
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