title: Conformational fluctuations versus constraints in amino acid side chains: the evolution of information content from free amino acids to proteins.
abstract: Like all other complex biological systems, proteins exhibit properties not found in free amino acids (i.e., emergent properties). Here, we explore top-down constraints experienced by the residue side chains in proteins compared to amino acids in increasingly complex molecular environments: free amino acids, end-capped amino acids, and the central residue in an alpha-helical nonapeptide. The crystalline structure of the contractile protein profilin Ib and the enzyme trypsin were chosen as objects of study, and submitted to 10 ns molecular dynamics (MD) simulations. The results revealed increased conformational constraints on the side chains when going from the simpler to the more complex compounds. A Shannon entropy (SE) analysis of the conformational behavior of the side chains showed in most cases a progressive and marked decrease in the SE of the chi1 and chi2 dihedral angles. This is equivalent to stating that conformational constraints on the side chain of residues increase their information content and, hence, recognition specificity compared to free amino acids. In other words, the vastly increased information content of a protein relative to its free monomers is embedded not only in the tertiary structure of the backbone, but also in the conformational behavior of the side chains. The postulated implication is that both backbone and side chains, by virtue of being conformationally constrained, contribute to the protein's recognition specificity toward other macromolecules and ligands.
authors.affiliation: Department of Medicinal Chemistry, Institute of Pharmacology of the Polish Academy of Sciences, 12 Smetna St., PL-31343 Krakow.
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Bojarski
authors.forename: Mateusz
authors.initials: M
authors.lastname: Nowak
authors.forename: Bernard
authors.initials: B
authors.lastname: Testa
mesh_terms: D000596:Amino Acids / Q000032:analysis / Q000737:chemistry*; D019143:Evolution, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000032:analysis / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D011506:Proteins