Paul Robustelli

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We present a method, CamShift, for the rapid and accurate prediction of NMR chemical shifts from protein structures. The calculations performed by CamShift are based on an approximate expression of the chemical shifts in terms of polynomial functions of interatomic distances. Since these functions are very fast to compute and readily differentiable, the(More)
Protein-folding intermediates have been implicated in amyloid fibril formation involved in neurodegenerative disorders. However, the structural mechanisms by which intermediates initiate fibrillar aggregation have remained largely elusive. To gain insight, we used relaxation dispersion nuclear magnetic resonance spectroscopy to determine the structure of a(More)
We introduce a procedure to determine the structures of proteins by incorporating NMR chemical shifts as structural restraints in molecular dynamics simulations. In this approach, the chemical shifts are expressed as differentiable functions of the atomic coordinates and used to compute forces to generate trajectories that lead to the reduction of the(More)
Many proteins can be partially or completely disordered under physiological conditions. Structural characterization of these disordered states using experimental methods can be challenging, since they are composed of a structurally heterogeneous ensemble of conformations rather than a single dominant conformation. Molecular dynamics (MD) simulations should(More)
A combination of NMR spectroscopy and molecular modeling has been employed to characterize the conformation and dynamics of the macrolide ring in verrucarin A and roridin A, two closely related toxins in the trichothecene mycotoxin family. Longitudinal carbon-13 relaxation times demonstrate the relative flexibility of the macrolide ring. The calculations,(More)
The 93-residue N-terminal fragment of apolipoprotein A-I (ApoA-I) is the major constituent of fibrils isolated from patients affected by the amyloidosis caused by ApoA-I mutations. We have prepared eight polypeptides corresponding to all the currently known amyloidogenic variants of the N-terminal region of ApoA-I, other than a truncation mutation, and(More)
In this investigation, semiempirical NMR chemical shift prediction methods are used to evaluate the dynamically averaged values of backbone chemical shifts obtained from unbiased molecular dynamics (MD) simulations of proteins. MD-averaged chemical shift predictions generally improve agreement with experimental values when compared to predictions made from(More)
Solid-state NMR spectroscopy does not require proteins to form crystalline or soluble samples and can thus be applied under a variety of conditions, including precipitates, gels, and microcrystals. It has recently been shown that NMR chemical shifts can be used to determine the structures of the native states of proteins in solution. By considering the(More)
The relationship between inherent internal conformational processes and enzymatic activity or thermodynamic stability of proteins has proven difficult to characterize. The study of homologous proteins with differing thermostabilities offers an especially useful approach for understanding the functional aspects of conformational dynamics. In particular,(More)
Molecular dynamics (MD) simulations have been employed to study the conformational dynamics of the partially disordered DNA binding basic leucine zipper domain of the yeast transcription factor GCN4. We demonstrate that back-calculated NMR chemical shifts and spin-relaxation data provide complementary probes of the structure and dynamics of disordered(More)