@article {101416,
	title = {Excluded volume in protein side-chain packing},
	journal = {Journal of Molecular Biology},
	volume = {311},
	year = {2001},
	month = {2001},
	pages = {183 - 193},
	abstract = {The excluded volume occupied by protein side-chains and the requirement of high packing density in the protein interior should severely limit the number of side-chain conformations compatible with a given native backbone. To examine the relationship between side-chain geometry and side-chain packing, we use an all-atom Monte Carlo simulation to sample the large space of side-chain conformations. We study three models of excluded volume and use umbrella sampling to effectively explore the entire space. We find that while excluded volume constraints reduce the size of conformational space by many orders of magnitude, the number of allowed conformations is still large. An average repacked conformation has 20 \% of its χ angles in a non-native state, a marked reduction from the expected 67 \% in the absence of excluded volume. Interestingly, well-packed conformations with up to 50 \% non-native χ angles exist. The repacked conformations have native packing density as measured by a standard Voronoi procedure. Entropy is distributed non-uniformly over positions, and we partially explain the observed distribution using rotamer probabilities derived from the Protein Data Bank database. In several cases, native rotamers that occur infrequently in the database are seen with high probability in our simulation, indicating that sequence-specific excluded volume interactions can stabilize rotamers that are rare for a given backbone. In spite of our finding that 65 \% of the native rotamers and 85 \% of χ1 angles can be predicted correctly on the basis of excluded volume only, 95 \% of positions can accommodate more than one rotamer in simulation. We estimate that, in order to quench the side-chain entropy observed in the presence of excluded volume interactions, other interactions (hydrophobic, polar, electrostatic) must provide an additional stabilization of at least 0.6 kT per residue in order to single out the native state.},
	url = {http://dx.doi.org/10.1006/jmbi.2001.4846},
	author = {Kussell, Edo and Shimada, Jun and Eugene I. Shakhnovich}
}
