Using Side‐Chain Aromatic Proton Chemical Shifts for a Quantitative Analysis of Protein Structures

Sahakyan, Aleksandr B.; Vranken, Wim; Cavalli, Andrea; Vendruscolo, Michele

doi:10.1002/ange.201101641

Cited by 2 publications

(2 citation statements)

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“…NMR spectroscopy is widely used to study the structure, dynamics, and interactions of proteins and nucleic acids. The chemical shift is one of the most abundant and precise outputs of an NMR experiment, and there has been significant progress in using chemical shifts to directly obtain structural and dynamic information of biomolecules (Cavalli et al, 2007,Sahakyan et al, 2011,Shen et al, 2008,Shen et al, 2009). However, a detailed interpretation of these NMR parameters is still a significant challenge due to the inherently complex dependence of chemical shifts on geometric, dynamic, and electronic properties.…”

Section: Introductionmentioning

confidence: 99%

AFNMR: automated fragmentation quantum mechanical calculation of NMR chemical shifts for biomolecules

et al. 2015

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We evaluate the performance of the automated fragmentation quantum mechanics/molecular mechanics approach (AF-QM/MM) on the calculation of protein and nucleic acid NMR chemical shifts. The AF-QM/MM approach models solvent effects implicitly through a set of surface charges computed using the Poisson-Boltzmann equation, and it can also be combined with an explicit solvent model through the placement of water molecules in the first solvation shell around the solute; the latter substantially improves the accuracy of chemical shift prediction of protons involved in hydrogen bonding with solvent. We also compare the performance of AF-QM/MM on proteins and nucleic acids with two leading empirical chemical shift prediction programs SHIFTS and SHIFTX2. Although the empirical programs outperform AF-QM/MM in predicting chemical shifts, the differences are in some cases small, and the latter can be applied to chemical shifts on biomolecules which are outside the training set employed by the empirical programs, such as structures containing ligands, metal centers, and non-standard residues. The AF-QM/MM described here is implemented in version 5 of the SHIFTS software, and is fully automated, so that only a structure in PDB format is required as input.

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Section: Introductionmentioning

confidence: 99%

AFNMR: automated fragmentation quantum mechanical calculation of NMR chemical shifts for biomolecules

et al. 2015

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“…Previously reported Karplus parameters (A, B, and C) were used for side-chain (Pé rez et al, 2001) and backbone angles (Vö geli et al, 2007), respectively. Methyl and aromatic chemical shifts were back predicted using CH3Shift (Sahakyan et al, 2011a) and ArShift (Sahakyan et al, 2011b) through Almost (Fu et al, 2014).…”

Section: Back-prediction Of Nmr Parameters From Structural Ensemblesmentioning

confidence: 99%

The Dynamic Basis for Signal Propagation in Human Pin1-WW

et al. 2016

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Allostery is the structural manifestation of information transduction in biomolecules. Its hallmark is conformational change induced by perturbations at a distal site. An increasing body of evidence demonstrates the presence of allostery in very flexible and even disordered proteins, encouraging a thermodynamic description of this phenomenon. Still, resolving such processes at atomic resolution is difficult. Here we establish a protocol to determine atomistic thermodynamic models of such systems using high-resolution solution state nuclear magnetic resonance data and extensive molecular simulations. Using this methodology, we study information transduction in the WW domain of a key cell-cycle regulator Pin1. Pin1 binds promiscuously to phospho-Ser/Thr-Pro motifs, however, disparate structural and dynamic responses have been reported upon binding different ligands. Our model consists of two topologically distinct states whose relative population may be specifically skewed by an incoming ligand. This model provides a canonical basis for the understanding of multi-functionality in Pin1.

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Using Side‐Chain Aromatic Proton Chemical Shifts for a Quantitative Analysis of Protein Structures

Cited by 2 publications

References 39 publications

AFNMR: automated fragmentation quantum mechanical calculation of NMR chemical shifts for biomolecules

AFNMR: automated fragmentation quantum mechanical calculation of NMR chemical shifts for biomolecules

The Dynamic Basis for Signal Propagation in Human Pin1-WW

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