Conformational constraints on side chains in protein residues increase their information content

Abstract

Like all other complex biological systems, proteins exhibit properties not seen in free amino acids (i.e., emergent properties). The present investigation arose from the deduction that proteins should offer a good model to approach the reverse phenomenon, namely top-down constraints experienced by protein residues compared to free amino acids. The crystalline structure of profilin Ib, a contractile protein of Acanthamoeba castellanii, was chosen as the object of study and submitted to 2-ns molecular dynamics simulation. The results revealed strong conformational constraints on the side chain of residues compared to the respective free amino acids. A Shannon entropy (SE) analysis of the conformational behavior of the side chains showed in most cases a strong decrease in the SE of the chi1 and chi2 dihedral angles compared to free amino acids. 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 recognition specificity of the protein toward other macromolecules and ligands.

Conformational Fluctuations versus Constraints in Amino Acid Side Chains: The Evolution of Information Content from Free Amino Acids to Proteins

“…This was, indeed, verified (data not shown) with the backbone of profilin Ib [15] and trypsin retaining a constant secondary structure during the 10-ns simulations and undergoing only limited oscillations in their tertiary structure.…”

“…± The molecular dynamics (MD) simulations reported here were carried out with two objectives in mind. The first objective was to confirm the results of a previous study [15], but with equilibrated Shannon entropies (SE) of torsion angles in side chains, and examining a second protein functionally diverse from the first one used. This objective has been fully met using longer (10 instead of 2 ns) simulation times.…”

“…A first deep question raised by these results concerns the relation, if any, between the emergence of protein-specific properties and the gain in information resulting from conformational constraints, a plausible hypothesis given the role of information exchange in complex biosystems [10]. In practical terms, we postulate that the increased information content of the side chain of residues compared to free amino acids contributes to the protein×s recognition specificity [15]. This hypothesis implies that the vastly increased information content of a protein relative to its free monomers is embedded not only in the tertiary structure of its backbone, but also in its side chains.…”

Dispersal (Entropy) and Recognition (Information) as Foundations of Emergence and Dissolvence

“…This is a question that can be investigated at the level of components due to their probabilistic behavior [11]. In a series of computational simulations using molecular mechanics [40,41], top-down constraints experienced by the side-chains of residues in proteins compared to free amino acids were explored. The results revealed increased conformational constraints on the side-chains of residues compared to the same amino acids in monomeric (free) form.…”

Simulations in Evolution. II. Relative Fitness and the Propagation of Mutants

“…Thus, if, for datasets 1 and 2, one finds that SE(2) < SE(1), this means that data set 2 contains more information than data set 1. Shannons theory is originally one of digital communication [6], but it is finding more and more applications in chemistry and biology [7] [8]. SE was calculated from these histograms using Eqn.…”