Professer Zan Luthey-Schulten's Lab has recently been highlighted in the Journal of the American Chemical Society (JACS) and Journal of Computational Chemistry.
JACS recently published the article “Capture and Quality Control Mechanisms for Adenosine-5′- triphosphate Binding” by Prof. Luthey-Schulten with Li Li (Center for Biophysics and Computational Biochemistry), Susan A. Martinis (Department of Biochemistry).
Abstract: The catalytic events in members of the nucleotidylyl transferase superfamily are initiated by a millisecond binding of ATP in the active site. Throughmetadynamics simulations on a class I aminoacyl-tRNA synthetase (aaRSs), the largest group in the superfamily, we calculate the free energy landscape of ATP selection and binding. Mutagenesis studies and fluorescence spectroscopy validated the identification of the most populated intermediate states. The rapid first binding step involves formation of encounter complexes captured through a fly-casting mechanism acting upon the triphosphate moiety of ATP. In the slower nucleoside binding step, a conserved histidine in the HxxH motif orients the incoming ATP through base-stacking interactions resulting in a deep minimum in the free energy surface. Mutation of this histidine significantly decreases the binding affinity measured experimentally and computationally. The metadynamics simulations further reveal an intermediate quality control state that the synthetases and most likely other members of the superfamily use to select ATP over other nucleoside triphosphates.
from Prof. Luthey-Schulten: We determined theoretically and verified experimentally the free energy and mechanism of ATP binding to the nucleotidylyl transferase superfamily of proteins. We could explain why ATP instead of GTP binds to this universal motif.
In the Journal of Computational Chemistry, the article "Lattice microbes: High-performance stochastic simulation method for the reaction-diffusion master equation"
The Article's Abstract: Spatial stochastic simulation is a valuable technique for studying reactions in biological systems. With the availability of high-performance computing (HPC), the method is poised to allow integration of data from structural, single-molecule and biochemical studies into coherent computational models of cells. Here, we introduce the Lattice Microbes software package for simulating such cell models on HPC systems. The software performs either well-stirred or spatially resolved stochastic simulations with approximatedcytoplasmic crowding in a fast and efficient manner. Our new algorithm efficiently samples the reaction-diffusion master equation using NVIDIA graphics processing units and is shown to be two orders of magnitude fasterthan exact sampling for large systems while maintaining an accuracy of ∼0.1%. Display of cell models and animation of reaction trajectories involving millions of molecules is facilitated using a plug-in to the popular VMD visualization platform. The Lattice Microbes software is open source and available for download at http://www.scs.illinois.edu/schulten/lm
In Summary, from Prof. Luthey-Schulten: We introduce the Lattice Microbes GPU based software package for simulating complex biochemical reaction networks on the level of the whole cell. Our approach integrates data from cyroelectron tomography, proteomics, and single molecule spectroscopy to capture the molecular crowding within cells. Lattice Microbe is being implemented on Blue Waters and other NSF/DOE supercomputer.