Showing papers by "Bruce Tidor published in 1990"
TL;DR: In this article, inelastic neutron scattering spectra are calculated from harmonic and damped harmonic models of the internal dynamics of a small protein, the bovine pancreatic trypsin inhibitor (BPTI).
Abstract: Inelastic neutron scattering spectra are calculated from harmonic and damped harmonic models of the internal dynamics of a small protein, the bovine pancreatic trypsin inhibitor (BPTI). Numerical Fourier transformation of the intermediate scattering function Fvibinc (q, t) is used to calculate the inelastic scattering. This permits the inclusion of multiphonon scattering and frictional damping effects. Although for a typical experimental configuration, the multiphonon contribution does not significantly alter the form of the scattering at frequencies below about 30 cm−1, it does have a significant effect on the scattering intensity at higher frequencies. Frictional damping is introduced into the harmonic model by assuming that each mode acts as an independent damped Langevin oscillator. With this model and the assumption that the lowest frequency modes are overdamped while the higher frequency modes are underdamped, improved agreement with the experimental BPTI powder results is obtained. The measured sca...
79 citations
TL;DR: Electrostatic effects play the dominant role in favoring dimerization of HbS compared with HbA; van der Waals interactions make a negligible contribution to the difference.
Abstract: Molecular dynamics simulations were performed to calculate the difference between the dimerization free energies of normal human deoxyhemoglobin (HbA) and the mutant sickle-cell deoxyhemoglobin HbS (Glu-beta 6----Val) for one of the lateral contacts in the HbS x-ray structure. The simulations yield a value of--15 kcal/mol. Although there is no quantitative experimental value for comparison, this is in qualitative agreement with the experimental result that HbS self-assembles into multistranded fibers that are responsible for erythrocyte sickling, while HbA does not. The free-energy difference was decomposed into enthalpic and entropic terms, both of which are significant, and the contributions of individual protein residues and of the solvent were examined. Electrostatic effects play the dominant role in favoring dimerization of HbS compared with HbA; van der Waals interactions make a negligible contribution to the difference. Both differential solvation and protein-protein interactions are important. Interactions within the donor tetramer (i.e., that containing the Glu-beta 6 mutation site), as well as those with the acceptor tetramer, contribute to the preferential free energy of dimerization of HbS.
41 citations