faculty

Assistant Professor of Chemistry and Assistant Research Professor in Bioinformatics
Ph.D., Boston University; Postdoctoral, Harvard University

Physical/ChemBio


Phone: (734) 763-8013     
E-mail: andricio@umich.edu

Research Group

Our research explores theoretical and computational topics at the interface between structural molecular biology and physical chemistry. It hinges on the central theme of developing and applying computer and modeling methods to describe, in terms of dynamics and thermodynamics, biologically important molecular processes, with the aim to complement, enhance or predict experimental findings. Research directions include:

Computer Simulations of DNA-Binding Machines. Protein-DNA interactions are essential in such crucial cellular functions as replication, repair, transcription or recombination. Many enzymes at and ahead of the replication fork affect large DNA fragments. For instance, topoisomerases undo DNA knotting. Others, like helicases and polymerases, are biomolecular motors: they use the energy of binding and/or hydrolysis of nucleotides to do mechanical work on the DNA fragments to which they bind. We have an avid interest in the theoretical description of these fundamental genetic processes through massively parallel computer simulations.

Dynamics-Function Relationships. Connections to NMR Relaxation. An accurate measure of free energy, important for protein/RNA stability or ligand binding, has to include the entropy manifested in molecular flexibility. On the experimental side, this dynamic aspect is brought in by developments in solution NMR spectroscopy, which measures motion by relaxation experiments. Molecular dynamics simulation is an important tool to complement these measurements and to connect dynamics to entropy.

Enhanced Sampling in Path Space. Many important equilibrium and kinetic properties of chemical systems (including proteins and nucleic acids) can be cast in terms of paths in multi-dimensional spaces. Sampling and optimization algorithms we have developed for the conformational space can be generalized and adapted to the space of paths. We see fertile ground for theoretical and computational work on several categories of paths, from chemical-reaction paths to paths in the sequence space of evolving proteins.

AWARDS

• National Science Foundation Career Award (2006)

REPRESENTATIVE PUBLICATIONS

1. J. Wereszczynski and I. Andricioaei, “On structural transitions, thermodynamic equilibrium and the phase diagram of DNA and RNA duplexes under external tension and torque,” PNAS, 103, 16200-16205 (2006)
   
2. P. Tian and I. Andricioaei, "Size, motion and function of the SecY translocon revealed by molecular dynamics simulations with virtual probes," Biophys. J. 90, 2718-2730 (2006).
   
3. C. Xing and I. Andricioaei, "On the calculation of time-correlation functions by potential scaling," J. Chem. Phys. 124, 034110 (2006)
   
4. L. Sari and I. Andricioaei, “Rotation of DNA around intact strand in human topoisomerase I implies distinct mechanisms for positive and negative supercoil relaxation,” Nucleic Acids Research 33, 6621-6634 (2005).
5. J. MacFadyen and I. Andricioaei, “A skewed-momenta method to efficiently generate conformational transition trajectories,” J. Chem. Phys. 123, 074107 (2005)
   
6. P. Tian and I. Andricioaei, “Repetitive pulling catalyzes co-translocational unfolding of barnase during import through a mitochondrial pore” J. Mol. Biol., 350 1017-1034 (2005).