Title: Local and Connected Voids in Protein Cores Reveal Random Close Packed Structure

Author (Talk): Jack Treado, Yale University

Abstract:

Dense packing in hydrophobic regions of protein cores is vital for protein stability. Recently, it has been shown that protein cores pack as densely as random systems of hard, purely repulsive amino acid-shaped particles compressed to Jamming [1]. This indicates that the underlying structure of a well-packed protein core is that of Random Close Packing (RCP). However, although protein cores and RCPs of amino acids share the same packing fraction, this does not necessarily imply that both systems share the same underlying packing structure. Here, we demonstrate structural equivalence between RCPs of amino acids and protein cores found in high resolution crystal structure using measures of local and non-local (i.e. "connected") void volumes. We find that local void volume distributions in proteins and packings fit a Gamma distribution with the same shape factor. We measure connected void percolation as a function of interior probe particle accessibility and find that both systems share the same percolation threshold and void cluster size distribution at the critical point. We demonstrate that these two measures of the void structure can distinguish packings of particles of varying geometries, indicating that similarity in the void distribution implies structural equivalence. Thus, RCPs of amino acids can serve as a mechanical analog of a protein core, and can aid in studying protein mechanical response to the presence of packing defects such as interior voids or cavities created by mutations. [1] Gaines, Jennifer C., W. Wendell Smith, Lynne Regan, and Corey S. O’Hern. “Random Close Packing in Protein Cores.” Physical Review E 93, no. 3 (March 28, 2016): 032415.