Packing in Protein Cores

Abstract

Proteins are biological polymers that underlie all cellular functions. The first high-resolution protein structures were determined by x-ray crystallography in the 1960s. Since then, there has been continued interest in understanding and predicting protein structure and stability. It is well-established that a large contribution to protein stability originates from the sequestration from solvent of hydrophobic residues in the protein core. How are such hydrophobic residues arranged in the core? And how can one best model the packing of these residues? Here we show that to properly model the packing of residues in protein cores it is essential that amino acids are represented by appropriately calibrated atom sizes, and that hydrogen atoms are explicitly included. We show that protein cores possess a packing fraction of $\varphi \approx 0.56$, which is significantly less than the typically quoted value of 0.74 obtained using the extended atom representation. We also compare the results for the packing of amino acids in protein cores to results obtained for jammed packings from disrete element simulations composed of spheres, elongated particles, and particles with bumpy surfaces. We show that amino acids in protein cores pack as densely as disordered jammed packings of particles with similar values for the aspect ratio and bumpiness as found for amino acids. Knowing the structural properties of protein cores is of both fundamental and practical importance. Practically, it enables the assessment of changes in the structure and stability of proteins arising from amino acid mutations (such as those identified as a result of the massive human genome sequencing efforts) and the design of new folded, stable proteins and protein-protein interactions with tunable specificity and affinity.

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Cited by in corpus (8)

• Hypostatic jammed packings of frictionless nonspherical particles
• Void distributions reveal structural link between jammed packings and protein cores
• Mechanical and Vibrational Properties of Three-Dimensional Dimer Packings Near the Jamming Transition
• Vibrational properties of two-dimensional dimer packings near the jamming transition
• Protein folding as a jamming transition
• The connection between polymer collapse and the onset of jamming
• Atomic Density Distributions in Proteins: Structural and Functional Implications
• The effect of stereochemical constraints on the structural properties of folded proteins