New protein parameters are reported for the all-atom empirical energy function in the CHARMM program. The parameter evaluation was based on a self-consistent approach designed to achieve a balance between the internal (bonding) and interaction (nonbonding) terms of the force field and among the solvent−solvent, solvent−solute, and solute−solute interactions. Optimization of the internal parameters used experimental gas-phase geometries, vibrational spectra, and torsional energy surfaces supplemented with ab initio results. The peptide backbone bonding parameters were optimized with respect to data for N-methylacetamide and the alanine dipeptide. The interaction parameters, particularly the atomic charges, were determined by fitting ab initio interaction energies and geometries of complexes between water and model compounds that represented the backbone and the various side chains. In addition, dipole moments, experimental heats and free energies of vaporization, solvation and sublimation, molecular volume...

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All-atom empirical potential for molecular modeling and dynamics studies of proteins.

http://www.jbc.org/content/276/7/5177.full.pdf

Mapping the pathways for O2 entry into and exit from myoglobin.

The 2.54 A resolution structure of Ni-Fe hydrogenase has revealed the existence of hydrophobic channels connecting the molecular surface to the active site. A crystallographic analysis of xenon binding together with molecular dynamics simulations of xenon and H2 diffusion in the enzyme interior suggest that these channels serve as pathways for gas access to the active site.

Gas access to the active site of Ni-Fe hydrogenases probed by X-ray crystallography and molecular dynamics.

Recently we reported that antibodies can generate hydrogen peroxide (H_2O_2) from singlet molecular oxygen (^1O_2^*). We now show that this process is catalytic, and we identify the electron source for a quasi-unlimited generation of H_2O_2. Antibodies produce up to 500 mole equivalents of H_2O_2 from^1O_2^*, without a reduction in rate, and we have excluded metals or Cl– as the electron source. On the basis of isotope incorporation experiments and kinetic data, we propose that antibodies use H_2O as an electron source, facilitating its addition to ^1O_2^* to form H_2O_3 as the first intermediate in a reaction cascade that eventually leads to H_2O_2. X-ray crystallographic studies with xenon point to putative conserved oxygen binding sites within the antibody fold where this chemistry could be initiated. Our findings suggest a protective function of immunoglobulins against ^1O_2^* and raise the question of whether the need to detoxify ^1O_2^* has played a decisive role in the evolution of the immunoglobulin fold.

https://science.sciencemag.org/content/sci/293/5536/1806.full.pdf

U.C. Singh

Papers

Protein-ligand dynamics: a 96 picosecond simulation of a myoglobin-xenon complex