Self-assembly of trimesic acid (TMA) displayed remarkable abundance over its full coverage range on gold
under ultrahigh vacuum conditions. Experiments showed that previously well-reported “chicken wire” and
“flower” structures were actually two special cases within its full coverage. All observed assembling structures
formed hexagonal porous networks that could be well-described by a unified model in which the TMA
molecules inside the half unit cells (equilateral triangles) were bound via trimeric hydrogen bonds and all
half unit cells were connected to each other via dimeric hydrogen bonds. These porous networks possessed
pores of 1.1 ± 0.1 nm in diameter, and the interpore distance was tunable from 1.6 nm on at a step size of
∼0.93 nm. Energetics analysis unveiled that the assembling structures less than one molecular layer was
optimally driven by maximization of the dimeric hydrogen bonds.
The binding of a series of hydroxamate inhibitors with gelatinase-A is examined to evaluate the viability of calculating free energies of binding, ∆G b , utilizing molecular dynamics (MD) simulations with a linear interaction energy approach. In our simulations, a bonded model was used to represent the potentials of the catalytic zinc center. The electrostatic distribution of this model was derived using a two-stage electrostatic potential fitting calculations. The resulting bonded model was then used to generate the MD trajectories. Coulombic, van der Waals, and coordinate bond energy components determined from MD simulations of the bound and unbound inhibitors solvated in water were correlated with the free energies of binding for the 15 hydroxamate inhibitors. In the correlation process, several linear models consisted of different energy components were tested. We found that besides the usually used Coulombic and van der Waals energy terms, the introduction of a constant term could significantly improve the correlation. The best model yields an average error of 0.6 kcal/mol for the 15 binding affinities, which cover an observed range of 7.2 kcal/mol. The predictive ability of the best model was revealed by the high value of q 2 (0.854) from the leave-one-out cross-validation. To this series of inhibitors, the constant term can be treated as effective adjustment to the entropy contribution in the binding free energies. The MD simulations predicted the binding mode of the gelatinase-A with the studied inhibitors, and also provided insights into the interactions occurring in the active site and the origins of variations in ∆G b . The P 1 ′ groups of inhibitors make extensive van der Waals and hydrophobic contacts with the nonpolar side chains of four residues in the S1′ subsite, including Leu 197, Val 198, Leu 218, and Tyr 223, which directly influence the ligand binding. Hydrogen bonds between hydroxamates and gelatinase-A are very important to stabilize the inhibitors in the active site. The hydrogen bonds between the P 3 ′ group and gelatinase-A can produce more favorable electrostatic interactions.
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