The origin and extent of coarse‐grained regularities in protein internal packing

Abstract

Despite the suitability of various lattice geometries for coarse-grained modeling of proteins, the actual packing geometry of residues in folded structures has remained largely unexplored. A strong tendency to assume a regular packing geometry is shown here by optimally reorienting and superimposing clusters of neighboring residues from databank structures examined on a coarsegrained (single-site-per-residue) scale. The orientation function (or order parameter) of the examined coordination clusters with respect to fcc lattice directions is found to be 0.82. The observed geometry, which may be termed an incomplete distorted face-centered cubic (fcc) packing, is apparently favored by the drive to maximize packing density, in a fashion analogous to the way identical spheres pack densely and follow fcc geometry. About 2/3 of all residues obey this packing geometry, while the remainder occupy other context-dependent positions. The preferred coordination directions show relatively small variations over the various amino acid types, consistent with uniform residue viewpoint. Both the extremes of solvent-exposed and completely buried residue neighborhoods approximate the same generic packing, the only difference being in the numbers (and not the orientations) of coordination sites that are occupied (or left void for solvent occupancy). We observe the prevalence of a rather uniform (tight) residue packing density throughout the structure, including even the residues packed near solvent-exposed regions. The observed orientation distribution reveals an underlying, intrinsic orientation lattice for proteins. Proteins 2003;52:56 -67.

An Amino Acid Packing Code for α-Helical Structure and Protein Design

“…The XY•H socket characterizes not only the packing innate to α-helical structure, but also the role that packing at the level of 2° structure has in establishing higher order 3° and 4° interactions. Although the XY•H socket motif is found in other models 19;24;29;32;33 as far back as Efimov 30;31 and notably Lim 27;28 , neither recognizes the socket as the primary motif to protein packing, but rather complicate the description of packing with more general combinations of other motifs. Because we had developed a precise vocabulary that exactly describes packing 1 , we could eliminate dependent packing groups that were redundant to the description of packing and derive that the single knob-socket motif describes α-helical packing.…”

Self-assembly dynamics for the transition of a globular aggregate to a fibril network of lysozyme proteins via a coarse-grained Monte Carlo simulation

“…It is rather easy to identify the residues that are least mobile at low temperature. For example, the least mobile residues in an isolated protein (Nc = 1, Figure 6) 22 D act like a nucleus (pinning center) for local coagulation of residues towards forming the globular structure of the protein. The pinning centers are mainly electrostatic residues (Asp (D), Glu (E), Lys (K), Arg (R)) along with a couple of hydrophobic residues (Cys (C)).…”

“…Knowledge-based residue-residue (KBRR) interactions which are based on the statistical analysis of ensembles involving thousands of protein structures available in the Protein Data Bank (PDB) have been used extensively in modeling protein structures for decades. [18][19][20][21][22][23][24][25] The enormity of the literature available on this subject does not allow us to cite an exhaustive list; we therefore cite only a few for historical perspective and that are especially relevant to the work presented here. We have employed KBRR interactions 5,14 such as the classical Miyazawa-Jernigan contact matrix 19 in studying the structure and dynamics of individual proteins as well as self-assembly of peptides 14 and proteins.…”

Globular structure of a human immunodeficiency virus-1 protease (1DIFA dimer) in an effective solvent medium by a Monte Carlo simulation

“…The last few decades have witnessed an enormous surge in interest [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] in modeling proteins. Much attention is focused on identifying the universal characteristics, e.g., folding pathways via analysis of the energy landscapes of protein chains as well as their specific characteristics that entail local structures to understand binding to pertinent targets.…”