Journal ArticleDOI
PROPKA3: Consistent Treatment of Internal and Surface Residues in Empirical pKa Predictions
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TLDR
The rules and parameters for one of the most commonly used empirical pKa predictors, PROPKA, are revised based on better physical description of the desolvation and dielectric response for the protein, and a new and consistent approach to interpolate the description between the previously distinct classifications into internal and surface residues is introduced.Abstract:
In this study, we have revised the rules and parameters for one of the most commonly used empirical pKa predictors, PROPKA, based on better physical description of the desolvation and dielectric response for the protein. We have introduced a new and consistent approach to interpolate the description between the previously distinct classifications into internal and surface residues, which otherwise is found to give rise to an erratic and discontinuous behavior. Since the goal of this study is to lay out the framework and validate the concept, it focuses on Asp and Glu residues where the protein pKa values and structures are assumed to be more reliable. The new and improved implementation is evaluated and discussed; it is found to agree better with experiment than the previous implementation (in parentheses): rmsd = 0.79 (0.91) for Asp and Glu, 0.75 (0.97) for Tyr, 0.65 (0.72) for Lys, and 1.00 (1.37) for His residues. The most significant advance, however, is in reducing the number of outliers and removing...read more
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Journal ArticleDOI
Improved Treatment of Ligands and Coupling Effects in Empirical Calculation and Rationalization of pKa Values.
TL;DR: A novel algorithm is presented that identifies noncovalently coupled ionizable groups, where pKa prediction may be especially difficult, which is a general improvement to PROPKA and is applied to proteins with and without ligands.
Journal ArticleDOI
Real-time shape approximation and fingerprinting of single proteins using a nanopore.
Erik Yusko,Brandon R. Bruhn,Olivia M. Eggenberger,Olivia M. Eggenberger,Jared Houghtaling,Jared Houghtaling,Ryan Rollings,Nathan Walsh,Santoshi Nandivada,Mariya A. Pindrus,Adam R. Hall,David Sept,Jiali Li,Devendra S. Kalonia,Michael Mayer,Michael Mayer +15 more
TL;DR: The zeptolitre sensing volume of bilayer-coated solid-state nanopores can be used to determine the approximate shape, volume, charge, rotational diffusion coefficient and dipole moment of individual proteins.
Journal ArticleDOI
The multiple roles of histidine in protein interactions
TL;DR: The coordinate interactions between histidine and metallic cations are the strongest one acting in broad range, followed by the cation-π, hydrogen-π), and π-π stacking interactions.
Journal ArticleDOI
Graphical analysis of pH-dependent properties of proteins predicted using PROPKA
TL;DR: The GUI considerably extends the analysis and validation possibilities of the PROPKA approach and can conveniently be used to investigate ionizable groups, and their interactions, of residues with significantly perturbed pKa values or residues that contribute to the stabilization energy the most.
Journal ArticleDOI
Structural basis of Smoothened regulation by its extracellular domains
Eamon F. X. Byrne,Ria Sircar,Paul S. Miller,George Hedger,Giovanni Luchetti,Sigrid Nachtergaele,Mark D. Tully,Laurel Mydock-McGrane,Douglas F. Covey,Robert P. Rambo,Mark S.P. Sansom,Simon Newstead,Rajat Rohatgi,Christian Siebold +13 more
TL;DR: The results clarify the structural mechanism by which the activity of a GPCR is controlled by ligand-regulated interactions between its extracellular and transmembrane domains.