The capabilities of the polarizable force fields for alchemical free energy calculations have been limited by the high computational cost and complexity of the underlying potential energy functions. In this work, we present a GPU based general alchemical free energy simulation platform for polarizable potential AMOEBA. Tinker-OpenMM, the OpenMM implementation of the AMOEBA simulation engine has been modified to enable both absolute and relative alchemical simulations on GPUs, which leads to a ~200-fold improvement in simulation speed over a single CPU core. We show that free energy values calculated using this platform agree with the results of Tinker simulations for the hydration of organic compounds and binding of host-guest systems within the statistical errors. In addition to absolute binding, we designed a relative alchemical approach for computing relative binding affinities of ligands to the same host, where a special path was applied to avoid numerical instability due to polarization between the different ligands that bind to the same site. This scheme is general and does not require ligands to have similar scaffolds. We show that relative hydration and binding free energy calculated using this approach match those computed from the absolute free energy approach.
Microbially produced alkanes are a new class of biofuels that closely match the chemical composition of petroleum-based fuels. Alkanes can be generated from the fatty acid biosynthetic pathway by the reduction of acyl-ACPs followed by decarbonylation of the resulting aldehydes. A current limitation of this pathway is the restricted product profile, which consists of n-alkanes of 13, 15, and 17 carbons in length. To expand the product profile, we incorporated a new part, FabH2 from Bacillus subtilis, an enzyme known to have a broader specificity profile for fatty acid initiation than the native FabH of Escherichia coli. When provided with the appropriate substrate, the addition of FabH2 resulted in an altered alkane product profile in which significant levels of n-alkanes of 14 and 16 carbons in length are produced. The production of even chain length alkanes represents initial steps toward the expansion of this recently discovered microbial alkane production pathway to synthesize complex fuels. This work was conceived and performed as part of the 2011 University of Washington international Genetically Engineered Machines (iGEM) project.
Aromatic molecules with π electrons
are commonly involved
in chemical and biological recognitions. For example, nucleobases
play central roles in DNA/RNA structure and their interactions with
proteins. The delocalization of the π electrons is responsible
for the high polarizability of aromatic molecules. In this work, the
AMOEBA force field has been developed and applied to 5 regular nucleobases
and 12 aromatic molecules. The permanent electrostatic energy is expressed
as atomic multipole interactions between atom pairs, and many-body
polarization is accounted for by mutually induced atomic dipoles.
We have systematically investigated aromatic ring stacking and aromatic-water
interactions for nucleobases and aromatic molecules, as well as base–base
hydrogen-bonding pair interactions, all at various distances and orientations.
van der Waals parameters were determined by comparison to the quantum
mechanical interaction energy of these dimers and fine-tuned using
condensed phase simulation. By comparing to quantum mechanical calculations,
we show that the resulting classical potential is able to accurately
describe molecular polarizability, molecular vibrational frequency,
and dimer interaction energy of these aromatic systems. Condensed
phase properties, including hydration free energy, liquid density,
and heat of vaporization, are also in good overall agreement with
experimental values. The structures of benzene liquid phase and benzene-water
solution were also investigated by simulation and compared with experimental
and PDB structure derived statistical results.
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