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Computer simulations of biological mac-romolecules allow detailed mechanistic studies of how structure and dynamics

relate to biological function. We are interest-ed both in the development of new simulation methods and their application to challenging biophysical problems. In particular we are fo-cused on employing multi-scale simulation methodologies that combine fully atomistic descriptions with coarse-grained models and

implicit mean-field descriptions of solvent environments. Such methods allow us to explore conformational dynamics over long time scales and across large spatial scales ranging from supramolecular assemblies all the way to cellular scales. The ultimate goal of our research is to bridge between our current understanding of single-molecule dynamics and biological function at the cellular level.

One area of specific interest involves protein-nucleic acid complexes that are involved in replica tion and transcription. We are studying the recognition of post-replication DNA mismatches by MutS and the human homolog MSH2-MSH6 and subse quent initiation of DNA repair. A detailed un derstanding of the DNA mismatch repair system is relevant for many types of cancer that often result from DNA mutations that are left un repaired. We are also interested in mechanistic details of how transcription is carried out by RNA polymerase because of its fundamental importance in biology.

A second area of emphasis is the study of membrane-bound proteins and peptides. Specific systems of interest are the regulation of Ca2+ transport in heart muscle by SERCA through interactions with phosholamban and the structure and dynamics of viral fusion peptides. Especially in the case of fusion peptides we are also interested in aggregation in the context of the membrane since oligomers appear to be critical for fusion activity.

A third area of interest is the prediction of protein structures from its amino acid sequence at levels of accuracy similar to

experimental data. While it has become relatively easy to generate native-like models if structural templates are available from related proteins, such models often lack detailed features of amino acid side chain packing in the native structure. We are applying enhanced sampling techniques in combination with accurate energy functions in order to refine approximate protein structures towards the actual native conformation.

SERCA Ca2+ pump regulated by phospholamban.

Multiscale modeling of biological macromolecules.

MSH2-MSH6 and RNA polymerase structures.

Structure refinement with lattice-based sampling.

Professor of Chemistry

and

Professor of BioChemistry & moleCular Biology

(b. 1969)Diplom, 1994, Technical Univ. of Berlin;Ph.D., 1999, Univ. of Houston;Postdoc, 1999-2003, The Scripps Research Institute.

517-432-7439

Computational Biochemistry

Michael Feig

RNA Polymerase II with Open and Closed Trigger Loops: Active Site Dynamics and Nucleic Acid Translocation, Michael Feig, Zachary F. Burton, Biophys. J. 2010, 99, 2577-2586.

Conformational Sampling of Influenza Fusion Peptide in Membrane Bilayers as a Function of Termini and Protonation States, Afra Panahi, Michael Feig, J. Phys. Chem. B 2010, 114, 1407-1416.

Effect of membrane thickness on confor-mational sampling of phospholamban from computer simulations, Maryam Sayadi, Seiichiro Tanizaki, Michael Feig, Biophys. J. 2010, 98, 805-814.

PRIMO/PRIMONA: A coarse-grained model for proteins and nucleic acids that pre-serves near-atomistic accuracy, Srinivasa M. Gopal, Shayantani Mukherjee, Yi-Ming Cheng, Michael Feig, Proteins 2010, 78, 1266-1281.

Sampling of near-native protein conforma-tions during protein structure refinement using a coarse-grained model, normal modes, and molecular dynamics simula-tions, Andrew Stumpff-Kane, Katarzyna Maksimiak, Michael S. Lee, Michael Feig, Proteins 2008, 70, 1345-1356.

Conformational Sampling of Peptides in Cellular Environments, Seiichiro Tanizaki, Jacob W. Clifford, Brian D. Connelly, Michael Feig, Biophys. J. 2008, 94, 747-759.

Selected PublicationS