Predicting interaction sites between glycolytic enzymes and cytoskeletal proteins employing concepts of the Molecular Recognition Theory

Abstract

In 1984 Blalock and Smith focused attention on certain complementary hydropathic relationships between amino acids based on the genetic code. Amino acids specified on one strand of DNA were found to be hydropathically complementary to those encoded by the opposite strand of the DNA in the same reading frame. This is so because the hydropathic character of an amino acid is determined by the second base of the triplet codon (A for hydrophilic and U for hydrophobic) with the identity of the amino acid determined by the first two bases. Consequently, peptide sequences derived from the noncoding strand of DNA, or RNA that is complementary to mRNA, will have an inverted pattern of hydropathy relative to the pattern of amino acids derived from the coding nucleic acid strand. These complementary peptides have been found more often than not to specifically bind to the partner peptide specified by the coding strand. This is the basis of the molecular recognition theory (MRT), as proposed by Blalock (see Blalock 1995) which hypothesizes “that complementary nucleotide sequences specify peptides or proteins that interact through complementary shapes or structures resulting from their inverted periodicity of hydrophobic and hydrophilic amino acids”.