417 Counting peptide-water hydrogen bonds in unfolded proteins
Haipeng Gong, Lauren L. Porter, and George D. Rose
It is known that a folded protein forms approximately two backbone hydrogen bonds per peptide unit, one acceptor for each amide hydrogen and one donor for each carbonyl oxygen. It is often assumed that the carbonyl oxygen forms an additional hydrogen bond when the protein unfolds, and the backbone is exposed to buffer. This assumption is based on the properties of small model compounds, like N-methylacetamide. If valid, a chain of N residues would lose approximately N backbone hydrogen bonds upon folding, a substantial deficit. Using exhaustive conformational sampling, Gong, et al. show that, in fact, the number of hydrogen bonds is essentially conserved between the folded and unfolded states.
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341 The dynameomics rotamer library: Amino acid side chain conformations and dynamics from comprehensive molecular dynamics simulations in water
Alexander D. Scouras and Valerie Daggett
Scouras and Daggett have recently completed molecular dynamics simulations of 807 different proteins representing essentially all of the known autonomous protein folds in an effort we refer to as Dynameomics. Here the authors focus on the analysis of the side chain conformations and dynamics of these 807 proteins to create a dynamic rotamer library. Overall the Dynameomics rotamer library offers a comprehensive depiction of side chain rotamer preferences and dynamics in solution. Compared with libraries derived from static structures, the Dynameomics rotamer library provides more realistic distributions for dynamic proteins in solution at ambient temperature, and importantly, charged surface residues are better represented.
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229 Exploring sparsely-populated states of macromolecules by diamagnetic and paramagnetic NMR relaxation
G. Marius Clore
Structural characterization of sparsely-populated intermediates is challenging because they generally cannot be trapped and are therefore invisible to conventional biophysical and structural techniques. Recent developments in NMR, involving the application of relaxation dispersion and paramagnetic relaxation enhancement, have opened the door to detect and visualize short-lived, spectroscopically “invisible” species under equilibrium conditions. Both techniques measure increases in line width for the major “visible” species arising from rapid exchange with the minor “invisible” species. Relaxation dispersion relies on differences in chemical shifts while paramagnetic relaxation enhancement is dependent on the presence of paramagnetic-nucleus distances that are shorter in the minor species than the major one. These techniques have shed fundamental new insights into a variety of biological processes including recognition, catalysis and protein folding.
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379 Structural determinants of ligand imprinting: A molecular dynamics simulation study of subtilisin in aqueous and apolar solvents
Diana Lousa, António M. Baptista, and Cláudio M. Soares
Enzymes in organic solvents appear to “remember” the presence of a ligand after it has been removed. This phenomenon is known as ligand imprinting and is not observed in water. How can ligand imprinting be explained at the molecular level? Using a theoretical methodology Lousa, et al. observed that because of the low flexibility exhibited in organic media, the enzyme retains the state induced by the ligand even when it has been removed. In water, the enzyme is more flexible and rapidly “forgets” the presence of the ligand.
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