Proteins can be viewed as small-world networks of amino acid residues connected through noncovalent interactions. Nuclear magnetic resonance chemical shift covariance analyses were used to identify long-range amino acid networks in the α subunit of tryptophan synthase both for the resting state (in the absence of substrate and product) and for the working state (during catalytic turnover). The amino acid networks observed stretch from the surface of the protein into the active site and are different between the resting and working states. Modification of surface residues on the network alters the structural dynamics of active-site residues over 25 Å away and leads to changes in catalytic rates. These findings demonstrate that amino acid networks, similar to those studied here, are likely important for coordinating structural changes necessary for enzyme function and regulation.

No abstract

Articles you may be interested inFree-energy analysis of the electron-density fluctuation in the quantum-mechanical/molecular-mechanical simulation combined with the theory of energy representation J. Chem. Phys. 136, 044505 (2012); 10.1063/1.3677184Computation of methodology-independent ionic solvation free energies from molecular simulations. II. The hydration free energy of the sodium cation Free energy of solvation from molecular dynamics simulation applying Voronoi-Delaunay triangulation to the cavity creation A free energy perturbation technique is described in which configurations from a classical simulation ͑molecular dynamics or Monte Carlo͒ with empirical solute-solvent interactions are used to calculate free energies with quantum mechanically derived solute-solvent interactions. This approach is much less costly than simulations with forces derived from quantum mechanics at each time step, since it only requires quantum energies to be calculated at classically determined configurations. The method is not limited to free energies of solvation, and can potentially be applied to calculations of activation energies and other condensed phase chemical transformations. As a test, this method was used to calculate the free energy of hydration of water at ambient conditions. With a good classical model the method gives accurate results with only 50 quantum calculations. The method is self-correcting in the sense that it can be used to recognize a bad classical model, and improved classical models can be derived by a least-squares fitting to the quantum energies. As a result, this method also provides novel information about the comparative strengths and weaknesses of classical solute models.

The thermodynamic feasibility of extracting CH4 gas from its hydrate clathrate by CO2 replacement is analyzed by molecular dynamics simulation. The approach to this investigation is the proof-of-principles and the development of the molecular tools to study the replacement equilibrium process. The effect of the water (model) description on the free energy of the replacement process is discussed and some relevant implications regarding the real process are addressed.