Dan Thomas Major

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Combined quantum mechanical/molecular mechanical simulations have been carried out to investigate the origin of the carbon acidity enhancement in the alanine racemization reaction catalyzed by alanine racemase (AlaR). The present study shows that the enhancement of carbon acidity of alpha-amino acids by the cofactor pyridoxal 5'-phosphate (PLP) with an(More)
We have carried out a mixed molecular dynamics and centroid path integral simulation using a combined quantum mechanical and molecular mechanical (QM/MM) potential to study the anomalous Brønsted relationship between rates and equilibria for deprotonation of nitroalkanes in water, which is known as the nitroalkane anomaly. The deprotonation process is(More)
The inclusion of nuclear quantum effects such as zero-point energy and tunneling is of great importance in studying condensed phase chemical reactions involving the transfer of protons, hydrogen atoms, and hydride ions. In the current work, we derive an efficient quantum simulation approach for the computation of the momentum distribution in condensed phase(More)
A bisection sampling method was implemented in path integral simulations of chemical reactions in solution in the framework of the quantized classical path approach. In the present study, we employ a combined quantum mechanical and molecular mechanical (QM/MM) potential to describe the potential energy surface and the path integral method to incorporate(More)
A bisection sampling method is implemented in the framework of a quantized classical path algorithm to include nuclear quantum effects in path integral simulations. The present study examines the convergence of these calculations on two model systems with respect to the number of beads used in the polymer chain and the number of configurations both in(More)
We report computational results of efficient catalysis of depro-tonation of L-alanine, by pyridoxal 5′-phosphate (PLP) and by alanine racemase (AlaR), which is the result of large solvation effects of the external aldimine cofactor to lower the pK a of the R-amino acid by 13 units and transition state stabilization (14.1 kcal/mol) by the enzyme. AlaR(More)
The inhibitory effect of ammonium glycyrrhizinate (AG) on crystallization of celecoxib (CXB) nanoparticles in aqueous medium was studied. CXB nanoparticles in powder form were prepared by rapid evaporation of all solvents from a volatile oil-in-water microemulsion. A powder containing 13 wt % CXB was obtained by immediate conversion of microemulsion(More)
In this review we give an overview of the field of Computational enzymology. We start by describing the birth of the field, with emphasis on the work of the 2013 chemistry Nobel Laureates. We then present key features of the state-of-the-art in the field, showing what theory, accompanied by experiments, has taught us so far about enzymes. We also briefly(More)
Terpene cyclases are responsible for the initial cyclization cascade in the multistep synthesis of more than 60,000 known natural products. This abundance of compounds is generated using a very limited pool of substrates based on linear isoprenoids. The astounding chemodiversity obtained by terpene cyclases suggests a tremendous catalytic challenge to these(More)