Michael Feig
Research Interests
We are using computational methods in order to study the structure,
dynamics, and energetics of biological macromolecules such as proteins
or nucleic acids. Our focus is concentrated in two areas: 1) The modeling
of large supramolecular assemblies in atomic detail and 2) the accurate
prediction of native protein structures.
As
an example of a supramolecular complex we are investigating the interaction
between the E.coli mismatch recognition protein MutS and DNA
with mismatched or missing base pairs. MutS recognizes defective DNA
after replication and initiates a multi-step process that leads to DNA
repair. A detailed understanding of the DNA mismatch repair system is
relevant for some types of cancer where the repair process is compromised.
Starting from crystal structures of the MutS protein-DNA complex we
apply computer simulation techniques to look at energetic and dynamic
aspects of this system.
The prediction of protein structures from sequence has seen great progress
through
recent methodological advances and the availability of an increasing
number of structural templates from experimental protein structures.
It is now often possible to generate approximate predictions that capture
many of the general features of the native fold. MORE
Recent Publications
Feig M, Sugita Y. 2012. Variable Interactions between Protein Crowders and Biomolecular Solutes Are Important in Understanding Cellular Crowding. J. Phys. Chem. B 116: 599-605.
Imamura D, Kuwana R, Kroos L, Feig M, Takamatsu H, Watabe K. Substrate specificity of SpoIIGA, a signal-transducing aspartic protease in Bacilli. 2011. J Biochem. 149(6):665-71.
Cho H, Mukherjee S, Palasuberniam P, Pillow L, Bilgin B, Nezich C, Walton SP, Feig M, Chan C. 2011. Molecular mechanism by which palmitate inhibits PKR autophosphorylation. Biochemistry. 50(6):1110-9.
Jaskierny AJ, Panahi A, Feig M. 2011. Effect of flanking residues on the conformational sampling of the internal fusion peptide from Ebola virus. Proteins. 79(4):1109-17.
Seibold SA, Singh BN, Zhang C, Kireeva M, Domecq C, Bouchard A, Nazione AM, Feig M, Cukier RI, Coulombe B, Kashlev M, Hampsey M, Burton ZF. 2010. Conformational coupling, bridge helix dynamics and active site dehydration in catalysis by RNA polymerase. Biochim Biophys Acta. 1799:575-587.
Yang W, Pollard M, Li-Beisson Y, Beisson F, Feig M, Ohlrogge J. A distinct type of glycerol-3-phosphate acyltransferase with sn-2 preference and phosphatase activity producing 2-monoacylglycerol. (2010) Proc Natl Acad Sci U S A. 107(26):12040-5.
A Panahi, M Feig. Conformational Sampling of Influenza Fusion Peptide in Membrane Bilayers as a Function of Termini and Protonation States. J. Phys. Chem. B (2010) 114 1407-1416.
Feig M, Burton ZF. RNA polymerase II flexibility during translocation from normal mode analysis. (2010) Proteins. 78 434-446.
Mukherjee S, Feig M. Conformational change in MSH2-MSH6 upon binding DNA coupled to ATPase activity. Biophys J. (2009) 96(11):L63-5.
Zavodszky MI, Stumpff-Kane AW, Lee DJ, Feig M. Scoring confidence index: statistical evaluation of ligand binding mode predictions. J Comput Aided Mol Des. (2009) 23(5):289-99.
Mukherjee S, Law SM, Feig M. Deciphering the mismatch recognition cycle in MutS and MSH2-MSH6 using normal-mode analysis. Biophys J. (2009) 96(5):1707-20.
