scholarly journals Too packed to change: site-specific substitution rates and side-chain packing in protein evolution

2014 ◽  
Author(s):  
María Laura Marcos ◽  
Julian Echave
Keyword(s):  
Protein Evolution ◽  
Packing Density ◽  
Main Chain ◽  
Side Chain ◽  
Side Chains ◽  
Contact Density ◽  
Chain Packing ◽  
Site Specific ◽  
Stress Theory ◽  
Side Chain Packing

In protein evolution, due to functional and biophysical constraints, the rates of amino acid substitution differ from site to site. Among the best predictors of site-specific rates is packing density. The packing density measure that best correlates with rates is the weighted contact number (WCN), the sum of inverse square distances between the site’s Cαand the other Cαs . According to a mechanistic stress model proposed recently, rates are determined by packing because mutating packed sites stresses and destabilizes the protein’s active conformation. While WCN is a measure of Cαpacking, mutations replace side chains, which prompted us to consider whether a site’s evolutionary divergence is constrained by main-chain packing or side-chain packing. To address this issue, we extended the stress theory to model side chains explicitly. The theory predicts that rates should depend solely on side-chain packing. We tested these predictions on a data set of structurally and functionally diverse monomeric enzymes. We found that, on average, side-chain contact density (WCNρ) explains 39.1% of among-sites rate variation, larger than main-chain contact density (WCNα) which explains 32.1%. More importantly, the independent contribution of WCNαis only 0.7%. Thus, as predicted by the stress theory, site-specific evolutionary rates are determined by side-chain packing.

Interrelations Between Side Chain and Main Chain Packing in Different Crystal Modifications of Alkoxylated Polyesters

2017 ◽  
Vol 121 (17) ◽  
pp. 4583-4591 ◽  
Author(s):  
Gaurav Gupta ◽  
Varun Danke ◽  
Tamoor Babur ◽  
Mario Beiner
Keyword(s):  
Main Chain ◽  
Side Chain ◽  
Chain Packing ◽  
Crystal Modifications

scholarly journals Packing of apolar side chains enables accurate design of highly stable membrane proteins

Science ◽  
2019 ◽  
Vol 363 (6434) ◽  
pp. 1418-1423 ◽  
Author(s):  
Marco Mravic ◽  
Jessica L. Thomaston ◽  
Maxwell Tucker ◽  
Paige E. Solomon ◽  
Lijun Liu ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Hydrophobic Effect ◽  
Side Chain ◽  
Side Chains ◽  
Chain Packing ◽  
Membrane Protein Folding ◽  
Natural Protein ◽  
Accurate Design ◽  
Polar Interactions ◽  
Packing Code

The features that stabilize the structures of membrane proteins remain poorly understood. Polar interactions contribute modestly, and the hydrophobic effect contributes little to the energetics of apolar side-chain packing in membranes. Disruption of steric packing can destabilize the native folds of membrane proteins, but is packing alone sufficient to drive folding in lipids? If so, then membrane proteins stabilized by this feature should be readily designed and structurally characterized—yet this has not been achieved. Through simulation of the natural protein phospholamban and redesign of variants, we define a steric packing code underlying its assembly. Synthetic membrane proteins designed using this code and stabilized entirely by apolar side chains conform to the intended fold. Although highly stable, the steric complementarity required for their folding is surprisingly stringent. Structural informatics shows that the designed packing motif recurs across the proteome, emphasizing a prominent role for precise apolar packing in membrane protein folding, stabilization, and evolution.

Side Chain Packing of the N- and C-Terminal Helices Plays a Critical Role in the Kinetics of CytochromecFolding†

Biochemistry ◽  
1996 ◽  
Vol 35 (17) ◽  
pp. 5538-5549 ◽  
Author(s):  
Wilfredo Colón ◽  
Gülnur A. Elöve ◽  
L. Paul Wakem ◽  
Fred Sherman ◽  
Heinrich Roder
Keyword(s):  
Critical Role ◽  
Side Chain ◽  
Chain Packing ◽  
Kinetics Of ◽  
Side Chain Packing

Effective dispersants for concentrated, nonaqueous suspensions

1992 ◽  
Vol 7 (10) ◽  
pp. 2884-2893 ◽  
Author(s):  
I. Sushumna ◽  
R.K. Gupta ◽  
E. Ruckenstein
Keyword(s):  
Main Chain ◽  
Side Chain ◽  
Solid Loading ◽  
Head Group ◽  
Side Chains ◽  
Concentrated Suspensions ◽  
Fatty Esters ◽  
Solids Loading ◽  
High Solids Loading ◽  
Order Of Magnitude

With the aim of identifying effective dispersants that would yield stable, high solids loading (≥60 vol.%) suspensions of oxides, carbides, or nitrides in nonaqueous carriers such as paraffinic oils, a number of dispersants were evaluated, using in most cases A16SG grade alumina from Alcoa as the filler. Among those evaluated were some common dispersants, such as menhaden fish oil and oleic acid, and commercial dispersants not commonly used in ceramic processing, such as polymeric fatty esters and petroleum sulfonates. More importantly, a few dispersants were synthesized and evaluated. The latter dispersants contained straight or cyclic (benzenic) side chains located far from the head group on 18 carbon main-chain fatty acid molecules. Among these, the dispersants with a 5–10 carbon side chain or with a benzenic side chain yielded very fluid suspensions (≥60 vol.%) compared to those with long polymeric or oligomeric side chains, or with no side chains, or the commercial dispersants; in some cases, for the same solid loading, the suspension viscosities were an order of magnitude lower with the synthesized side chain dispersants. These results indicate that molecules with an optimum side chain length located sufficiently far from the head group and an optimum backbone (main chain) constitute the most effective dispersants for concentrated suspensions. By combining the advantages provided by wider particle size distributions and by these effective dispersants, suspensions highly concentrated (up to 74 vol.%), and yet processable and “flowing” paste-like have been prepared.

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