Amino acid empirical contact energy definitions for fold recognition in the space of contact maps

BACKGROUND: Contradicting evidence has been presented in the literature concerning the effectiveness of empirical contact energies for fold recognition. Empirical contact energies are calculated on the basis of information available from selected protein structures, with respect to a defined reference state, according to the quasi-chemical approximation. Protein-solvent interactions are estimated from residue solvent accessibility. RESULTS: In the approach presented here, contact energies are derived from the potential of mean force theory, several definitions of contact are examined and their performance in fold recognition is evaluated on sets of decoy structures. The best definition of contact is tested, on a more realistic scenario, on all predictions including sidechains accepted in the CASP4 experiment. In 30 out of 35 cases the native structure is correctly recognized and best predictions are usually found among the 10 lowest energy predictions. CONCLUSION: The definition of contact based on van der Waals radii of alpha carbon and side chain heavy atoms is seen to perform better than other definitions involving only alpha carbons, only beta carbons, all heavy atoms or only backbone atoms. An important prerequisite for the applicability of the approach is that the protein structure under study should not exhibit anomalous solvent accessibility, compared to soluble proteins whose structure is deposited in the Protein Data Bank. The combined evaluation of a solvent accessibility parameter and contact energy allows for an effective gross screening of predictive models

Correction: Exploring exchange processes in proteins by paramagnetic perturbation of NMR spectra

Correction for 'Exploring exchange processes in proteins by paramagnetic perturbation of NMR spectra' by Yamanappa Hunashal et al., Phys. Chem. Chem. Phys., 2020, 22, 6247–6259, DOI: 10.1039/c9cp06950j

Protocol for MM/PBSA Molecular Dynamics Simulations of Proteins

Continuum solvent models have been employed in past years for understanding processes such as protein folding or biomolecular association. In the last decade, several attempts have been made to merge atomic detail molecular dynamics simulations with solvent continuum models. Among continuum models, the Poisson-Boltzmann solvent accessible surface area model is one of the oldest and most fundamental. Notwithstanding its wide usage for simulation of biomolecular electrostatic potential, the Poisson-Boltzmann equation has been very seldom used to obtain solvation forces for molecular dynamics simulation. We propose here a fast and reliable methodology to implement continuum forces in standard molecular mechanics and dynamics algorithms. Results for a totally unrestrained 1 ns molecular dynamics simulation of a small protein are quantitatively similar to results obtained by explicit solvent molecular dynamics simulations

Probing Protein Structure by Solvent Perturbation of NMR Spectra. I. A comparison with photo-CIDNP techniques applied to native a-lactalbumin

We have suggested elsewhere the use of surface mapping by spin label probes (Esposito et al., 1992). According to this approach, soluble nitroxides are added to a protein solution. Resonances of protons that are accessible to the nitroxide are broadened and bleached out of the spectrum, while resonances in the protein interior remain unaffected. This approach is, in principle, complementary to another technique, photochemically induced dynamic nuclear polarization, which maps the position of aromatic protons on the protein surface. A detailed comparison between the two techniques is necessary for a confident use of the more recent suggested nitroxide perturbation approach. In the present study, we show that the results obtained by the two techniques for the native state of bovine alpha-lactalbumin are fully consistent and may therefore be combined for the study of protein surfaces

NMR Investigation of Lipophilic Cage Ligands. Part 2. Structural Assignments and Conformational Properties of the Ligand 12-hexadecyl-7,17,22,27-tetraoxa-1,4,10,14-tetraazatricyclo (12.5.5.54,10) nonacosane and of its Sodium, Potassium & Silver Complexes

Two-dimensional homonuclear (COSY, phase-sensitive double quantum filtered COSY) and heteronuclear shift correlated experiments were employed to characterize fully the cylindrical cage ligand 12-hexadecyl-7,17,22,27-tetraoxa-1,4,10,14-tetraazatricyclo[12.5.5.54,10] nonacosane (1) and its sodium, potassium and silver complexes. 13C NMR variable temperature experiments indicated that the free ligand 1 is a mobile molecule in a fast conformational equilibrium at room temperature, whereas its sodium complex is more rigid, some degrees of freedom being allowed in that part of the molecule featuring the longest bridge. The potassium derivative behaves similarly to its sodium counterpart. For the silver complex the differences observed have been attributed to a stronger interaction of the metal ion with nitrogen atoms

Dynamics of a Globular Protein Adsorbed to Liposomal Nanoparticles

International audienceA solution-state NMR method is proposed to investigate the dynamics of proteins that undergo reversible association with nanoparticles (NPs). We applied the recently developed dark-state exchange saturation transfer experiment to obtain residue-level dynamic information on a NP-adsorbed protein in the form of transverse spin relaxation rates, R-2(bound). Based on dynamic light scattering, fluorescence, circular dichroism, and NMR spectroscopy data, we show that the test protein, human liver fatty acid binding protein, interacts reversibly and peripherally with liposomal NPs without experiencing significant structural changes. The significant but modest saturation transfer from the bound state observed at 14.1 and 23.5 T static magnetic fields, and the small determined R-2(bound) values were consistent with a largely unrestricted global motion at the lipid surface. Amino acid residues displaying faster spin relaxation mapped to a region that could represent the epitope of interaction with an extended phospholipid chain constituting the protein anchor. These results prove that atomic-resolution protein dynamics is accessible even after association with NPs, supporting the use of saturation transfer methods as powerful tools in bionanoscience