Arieh Warshel

Arieh Warshel is a distinguished professor of chemistry and biochemistry at the Dornsife College of Arts, Letters and Sciences, and the holder of the Dana and David Dornsife chair in chemistry. Awarded the 2013 Nobel Prize in Chemistry, along with Michael Levitt and Martin Karplus, for the development of multiscale models for complex chemical systems, Warshel is among the world leaders in computational biophysics and considered to be the founder of computational enzymology.

Warshel and his coworkers have pioneered key approaches for simulating the functions of biological molecules, including introducing molecular dynamics in biology, developing the quantum mechanical/molecular-mechanical (QM/MM) approach, introducing simulations of enzymatic reactions, pioneering microscopic simulations of electron transfer and proton transfer processes in solutions and proteins, pioneering microscopic modeling of electrostatic effects in macromolecules, and introducing simulations of protein folding. Recently, he and his coworkers have elucidated the energy molecular origin of the vectorial action of different molecular machines.

Warshel has utilized the university’s high-performance computing cluster (HPC) since its inception in 2000, performing advanced simulations of the functions of the biological, focusing on correlating molecular structures and the underlying energy landscapes and the resulting biological activity. As the result of Warshel’s developments in computer simulations of biological processes, questions about the functions of particular biological systems can now be formulated as well-defined problems in computational chemistry, ranging from enzyme design to ion flow in ion channels and to the action of molecular motors. Warshel’s simulation methods enable researchers to arrive at quantitative conclusions about such processes and provide the basis for fundamental advances in biophysics, and eventually, for practical advances in medicine.

Warshel is a Member of the USA National Academy of Sciences and an honorary member of the royal Society of Chemistry. He has also received numerous awards, including the Tolman Medal from the Southern California section of the American Chemical Society in 2003, the Royal Society of Chemistry (RSC) 2012 Soft Matter and Biophysical Chemistry Award, and the 2014 Founders Award of the Biophysical Society.

WarshelFigFO_500

ABOVE: We are working to understand the physical and chemical underpinnings of the unidirectional rotation of the F0-ATPase motor coupled to proton transport through the membrane. Coarse-grained modeling of the membrane embedded F0, along with the electrostatic free energy calculation of the proton transport pathway, reveal novel facts about this biological motor.

Earlier studies have mostly highlighted the role of the centrally conserved Asp-Arg ion pair to play a decisive role in directional rotation. But our results suggest that the proton transport free energy is asymmetric with respect to the left and right side of the central Asp-Arg ion pair, which is the underlying cause for unidirectional rotation of the c-ring from left to right (Mukherjee & Warshel, PNAS, 2012).