Instruct: Identify the main and secondary category of Arxiv papers based on the titles and abstracts
Query: Dissecting the roles of local packing density and longer-range effects
  in protein sequence evolution   What are the structural determinants of protein sequence evolution? A number
of site-specific structural characteristics have been proposed, most of which
are broadly related to either the density of contacts or the solvent
accessibility of individual residues. Most importantly, there has been
disagreement in the literature over the relative importance of solvent
accessibility and local packing density for explaining site-specific sequence
variability in proteins. We show here that this discussion has been confounded
by the definition of local packing density. The most commonly used measures of
local packing, such as the contact number and the weighted contact number,
represent by definition the combined effects of local packing density and
longer-range effects. As an alternative, we here propose a truly local measure
of packing density around a single residue, based on the Voronoi cell volume.
We show that the Voronoi cell volume, when calculated relative to the geometric
center of amino-acid side chains, behaves nearly identically to the relative
solvent accessibility, and both can explain, on average, approximately 34\% of
the site-specific variation in evolutionary rate in a data set of 209 enzymes.
An additional 10\% of variation can be explained by non-local effects that are
captured in the weighted contact number. Consequently, evolutionary variation
at a site is determined by the combined action of the immediate amino-acid
neighbors of that site and of effects mediated by more distant amino acids. We
conclude that instead of contrasting solvent accessibility and local packing
density, future research should emphasize the relative importance of immediate
contacts and longer-range effects on evolutionary variation.

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The categories of this paper are: dg-ga
11
The categories of this paper are: hep-lat
26
The categories of this paper are: bayes-an
36
The categories of this paper are: cmp-lg
15
The categories of this paper are: nucl-ex
20
The categories of this paper are: acc-phys
14
The categories of this paper are: math-ph
29
The categories of this paper are: funct-an
4
The categories of this paper are: cond-mat
32
The categories of this paper are: atom-ph
12
The categories of this paper are: nucl-th
6
The categories of this paper are: astro-ph
19
The categories of this paper are: eess
35
The categories of this paper are: mtrl-th
0
The categories of this paper are: hep-ph
5
The categories of this paper are: gr-qc