Carl Shirts
Associate Professor
Chemical and Biological Engineering


Research Interests

Understanding and designing materials at the molecular scale:

We work with experimentalists to better understand the molecular details of protein purification materials, water filtration membranes, and nanotextured surfaces, and to suggest novel improvements. The wide physical and chemical diversity of biomolecular processes strongly suggests that the possibilities for novel function in human-engineered materials are far, far beyond our current capabilities. Designed materials can draw from a much larger range of chemical structure and functionality than exists biologically; if we can add significant chemical diversity to nature's already impressive toolkit, what else can be created? Computational approaches provide a vitally important tool to help explore this enormously large materials space.

Computed-aided drug design:

Drug resistance is one of the biggest challenges in the pharmacological treatment of infectious diseases, and current informatics based drug discovery methods are not well-suited to rapidly develop new drug variants that can successfully overcome resistance. Our research has demonstrated that statistical mechanical methods can predict ligand binding affinities to within 1 kcal/mol in simple atomistically detailed systems, a level that becomes useful for the pharmaceutical industry. However, significant effort is necessary to make such methods work in more typical drug systems and to make them scale efficiently enough to be useful in general practice.  We work together with experimental researchers, software developers, and pharmaceutical companies to make computational drug design a reality, helping bring down the cost of developing cures to a host of diseases.

Improvements in molecular simulation and property prediction for engineering:

The two most pressing problems holding back improved atomic-level simulation of polymers, macromolecules, and other complicated dense fluids are the lack of sufficient sampling to accurately measure and observe molecular phenomena, and the choice of model parameters used to perform the simulations. It is currently only possible to simulate the equivalent of a few microseconds of all but the smallest biological systems, with some heroically expensive extensions to milliseconds with large supercomputers. Without sufficient conformational sampling, it is impossible even to verify if models are sufficiently faithful to experiment, let alone explore behavior of either long time scales or of larger molecular systems. Without good model parameters, atomistic predictions are unreliable and misleading, and developing new parameters is a labor-intensive process with significant guesswork. In the Shirts group, we research improved configurational sampling methods for macromolecules and more automated, statistically based methods for choosing molecular model parameters. These tools have the potential to assist researchers performing molecular simulation in all fields.


A.B., Harvard University (1999)
Ph.D., Stanford University (2005)
Post-doctoral Research Position, Columbia University (2005-2008)

  • NSF CAREER Award (2014)
  • American Chemical Society COMP OpenEye Outstanding Junior Faculty Award (2012)
  • Oak Ridge Associated Universities Ralph E. Powe, Jr. Faculty Enhancement Award (2009)
  • University of Virginia FEST Distinguished Young Investigator Award (2009)
  • National Institutes of Health Individual Postdoctoral Fellow, Ruth L. Kirschstein NRSA (2005-2008)
  • Fannie and John Hertz Graduate Fellowship (1999-2004)

J. E. Basconi, G. Carta and M. R. Shirts, "Effects of polymer graft properties on protein adsorption and transport in ion exchange chromatography: a multi-scale modeling study," Langmuir. 31(14), 4176­4187 (2015).

E. D. Zhong and M. R. Shirts, "Thermodynamics of coupled protein adsorption and stability using hybrid Monte Carlo simulations," Langmuir 30(17), 4952­4961 (2014).

J. I. Monroe, W. G. El-Nahal and M. R. Shirts, "Investigating the mutation resistance of non- nucleoside inhibitors of HIV-RT using multiple microsecond atomistic simulations," Proteins 82(1), 130­144 (2014).

C. M. Payne, W. Jiang, M. R. Shirts, M. E. Himmel, M. F. Crowley and G. T. Beckham, "Glycoside hydrolase processivity is directly related to oligosaccharide binding free energy," J. Am. Chem. Soc., 135(50), 18831­18839 (2013).

K. Wang, Y. Yang, J. D. Chodera and M. R. Shirts, "Identifying ligand binding sites and poses using GPU-accelerated Hamiltonian replica exchange molecular dynamics," J. Comput. Aid. Mol. Des. 27 (12), 989­1007 (2013).

H. Paliwal and M. R. Shirts, "Using multistate reweighting to rapidly and efficiently explore molecu- lar simulation parameters space for nonbonded interactions," J. Chem. Theory Comput., 9 (11), 4700­-4717 (2013).

M. R. Shirts, "Simple Quantitative Tests to Validate Sampling from Thermodynamic Ensembles," J. Chem. Theory Comput., 9 (2), 909­926 (2013).

T. T. Pham and M. R. Shirts, "Optimal pairwise and non-pairwise alchemical pathways for free ener- gy calculations of molecular transformation in solution phase," J. Chem. Phys., 136 (12), 124120 (2012).

J. D. Chodera and M. R. Shirts, "Replica exchange and expanded ensemble simulations as Gibbs sampling: Simple improvements for enhanced mixing," J. Chem. Phys., 135 (19), 194110 (2011).