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Bernhardt Trout, Ph.D.

Department of Chemical Engineering
Associate Professor of Chemical Engineering

Room E19-502B
617-258-5021 (phone)


Ph.D. Chemical Engineering, 1996
University of California, Berkeley

Research Summary

The Molecular Engineering Laboratory at MIT, led by PI Bernhardt L. Trout, develops and applies sophisticated computational, theoretical, and experimental methods in order to probe complex chemical systems on the molecular level and engineer them for high value chemical applications with maximum specificity. Applications are currently in the fields of biopharmaceutical formulation, energy and the environment, and nucleation and crystallization. In parallel, we develop new computational methods which are generally applicable for the engineering of complex chemical systems.

Biopharmaceutical Formulation
Biopharmaceuticals are complex, metastable protein/antibody molecules. Ideally, they should be delivered to patients in as high a concentration as possible in aqueous solution. From the moment that they are placed in solution, however, they degrade, the most problematic routes of degradation being aggregation, oxidation, and deamidation. We have worked in all three areas, elucidating mechanisms, developing predictive strategies, and inventing a completely new approach to prevent aggregation.

Energy and the Environment
Energy and the environment are two of the most crucial issues facing humanity in the 21st century. Supply of energy is correlated directly to economic growth and all the benefits thereof. Use of energy, however, leads to pollution. In these areas, the Molecular Engineering Laboratory at MIT focuses on new fuel sources, fuel transportation, and abatement of pollution.

Nucleation and Crystallization
Nucleation and crystallization are essential to the pharmaceutical industry, in addition to other industries. They are, however, currently more of a black art than a science, as the design of processes involving them is based on heuristic knowledge and rules of thumb. We are developing a mechanistic understanding of these processes with the objective of helping industrial sponsors engineering their processes based on rational understanding.

Methodology Development
In order to achieve the goals discussed above, sophisticated new methods are being developed in the Molecular Engineering Laboratory at MIT. These include highly efficient and accurate solvation methods, reaction path methods, and algorithms to correlating stability of complex molecules to molecular properties.

Most of our research is industrially funded, since we aim towards new technology development. Current and past partners, include, Amgen, DuPont, EniTecnologie, Ford Motor Company, Merck & Company, Inc., and others. Governmental sponsors include the NSF, NIH, DOE, and the Government of Singapore. Prof. Bernhardt L. Trout also consults for major biotechnology, pharmaceutical, and chemical companies.

Selected Publications

  • Baynes, B.M. and Trout, B.L., "Rational design of solution additives for the prevention of protein aggregation," Biophys. J., 87, 1631 (2004).
  • Chu, J.W., Wang, D.I.C. and Trout, B.L., "Molecular dynamic simulations and experimental oxidation rates of methionine residues of granulocyte colony-stimulating factor (G-CSF) at different pH values," Biochemistry, 43, 1019 (2004).
  • Baynes, B.M. and Trout, B.L., "Proteins in mixed solvents: a molecular-level perspective," J. Phys. Chem. B, 107, 14058 (2003).
  • Chu, J.W. and Trout, B.L., "On the mechanisms of peroxide oxidation in aqueous solutions: ab initio studies of hydrogen transfer of hydrogen peroxide and dimethyl sulfide oxidation by H2O2," J.A.C.S., 126, 900 (2004).
  • Chu, J.W., Trout, B.L., and Brooks, B.R., "A super-linear minimization scheme for the nudged elastic band method," J. Chem. Phys., 119, 12708 (2003).
  • Radhakrishnan, R. and Trout, B.L., "Nucleation of hexagonal (Ih) ice in liquid water," J.A.C.S., 125, 7743 (2003).
  • Radhakrishnan, R. and Trout, B.L., "Nucleation of crystalline phases of water in homogeneous and inhomogeneous environments," Phys. Rev. Lett., 90, 158301 (2003).
  • Chu, J.W., Brooks, B.R. and Trout, B.L, "Oxidation of methionine residues in aqueous solutions, free methionine and methionine in G-CSF," J.A.C.S., in press.
  • Anderson, B., Tester, J. W., and Trout, B. L., "Accurate potenials for argon - water and methane - water interactions via ab initio methods and their application to clathrate hydrates," J. Phys. Chem. B., 108, 16705 (2004).
  • Yin, J., Chu, J.W., Speed Ricci, M., Brems, D.N., Wang, D.I.C. and Trout, B.L., "Effects of antioxidants on the non-site-specific oxidation of methionine residues in granulocyte colonystimulating factor (G-CSF) and human parathyroid hormone (hPTH) fragment 13-34," Pharm. Res., 21,2378 (2004).
  • Chu, J.W., Yin, J., Brooks, B.R., Wang, D.I.C., Speed Ricci, M., Brems, D.N. and Trout, B.L., "A comprehensive picture of non-site-specific oxidation of methionine residues by peroxides in protein pharmaceuticals," J. Pharm. Sci., 93, 3096 (2004).
  • Gu, C., Lustig, S., and Trout, B.L., Solvation model based on order parameters and a fast sampling method for the calculation of solvation free energies of peptides, J. Phys. Chem. B, 110, 1476 (2006).
  • Baynes, B.M., Wang, D.I.C., and Trout, B.L., The role of arginine in the stabilization of proteins against aggregation, Biochemistry, 44, 4919 (2005).
  • Radhakrishnan, R. and Trout, B.L. Order parameter approach to understanding and quantifying the physico-chemical behavior of complex systems, in Handbook of Materials Modeling, Part B, Chapter 5: Rate Processes, Section 5.5, Dordrecht, The Netherlands: Springer, 2005.
  • Yin, J., Chu, J.W., Speed Ricci, M., Brems, D.N., Wang, D.I.C. and Trout, B.L., Effects of excipients on the hydrogen peroxide induced oxidation of methionine residues in granulocyte colony-stimulating factor (G-CSF), Pharm. Res., 22, 141 (2005).

Last Updated: April 16, 2008