Ioan AndricioaeiAssociate Professor, Chemistry |
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Research Interests |
Theoretical Chemistry and Biophysics | |
| URL | Group Web Page | |
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Academic Distinctions | National Science Foundation Career Award, 2006 | |
| Appointments | Harvard University, 1999-2003 | |
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Research Abstract |
Our research explores theoretical and computational topics at the interface between molecular biophysics and physical chemistry. It hinges on a two-fold central theme: (1) developing novel theoretical techniques and (2) 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: Enhanced Sampling in Trajectory 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. We have developed a set of trajectory reweighting techniques based on a stochastic path integral formalism that is particularly useful to treat both computer simulations and single-molecule experimental traces. 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. Another example is the machinery that compacts DNA inside the capsid of viruses. 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. |
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| Publications | M. Mills, B. Orr, M.M. Banaszak Holl and I. Andricioaei, "Microscopic Basis for the Mesoscopic Extensibility of Dendrimer-Compacted DNA," Biophys. J. (2009, accepted) | |
| C. Musselman, Q. Zhang, H.M. Al-Hashimi and I. Andricioaei, A referencing strategy for the direct comparison of nuclear magnetic resonance and molecular dynamics motional parameters in RNA, J. Phys. Chem. B (2009, in press) | ||
| A.T. Frank, A.C. Stelzer, H.M. Al-Hashimi and I. Andricioaei, Constructing RNA dynamical ensembles by combining MD and motionally decoupled NMR RDCs: New insights into RNA dynamics and adaptive ligand recognition, Nucleic Acids Res. 37, 3670-3679 (2009). | ||
| J. Nummela and I. Andricioaei, Energy landscape for DNA rotation and sliding through a phage portal, Biophys.J. (Letter) 96, L29-L31 (2009). | ||
| M. Mills and I. Andricioaei, "An Experimentally Guided Umbrella Sampling Protocol for Biomolecules" J. Chem. Phys. 129, 114101 (2008) | ||
| E.A. Dethoff, A.L. Hansen, C. Musselman, E.D. Watt, I. Andricioaei and H.M. Al-Hashimi, "Characterizing Complex Dynamics in the Transactivation Response Element Apical Loop and Motional Correlations with the Bulge by NMR, Molecular Dynamics, and Mutagenesis," Biophys. J. 95 3906-3915 (2008) | ||
| C.V. Kelly, P. R. Leroueil, E.K. Nett, J. Wereszczynski, J.R. Baker, B. G. Orr, M.M. Banaszak Holl and I. Andricioaei, "Poly(amidoamine) Dendrimers on Lipid Bilayers I: Free Energy and Conformation of Binding," J. Phys. Chem. B 112, 9337-9345 (2008). | ||
| C.V. Kelly, P. R. Leroueil, B. G. Orr, M.M. Banaszak Holl and I. Andricioaei, "Poly(amidoamine) Dendrimers on Lipid Bilayers II: Effects of Bilayer Phase and Dendrimer Termination," J. Phys. Chem. B 112, 9346-9353 (2008). | ||
| J. MacFadyen, J. Wereszczynski and I. Andricioaei, Directionally negative friction: A method for enhanced sampling of rare events J. Chem. Phys. 128, 114112 (2008) | ||
| J. Nummela, F. Yassin and I. Andricioaei, Entropy-enthalpy decomposition from nonequilibrium work trajectories, J. Chem. Phys. 128, 024104 (2008) | ||
| C. Musselman, H.M. Al-Hashimi and I. Andricioaei, iRED analysis of TAR RNA reveals motional coupling, long-range correlations, and a dynamical hinge, Biophys. J. 93, 411-422 (2007) | ||
| J. Nummela and I. Andricioaei, Exact low-force kinetics from high-force single-molecule unfolding events, Biophys. J. 93, 3373-3381 (2007) | ||
| I. Andricioaei, Specialized methods for improving ergodic sampling using molecular dynamics and Monte Carlo simulations Chapter 8 in Free Energy Calculations: Theory and Applications in Chemistry and Biology, pp. 277-322 , eds. A. Pohorille and C. Chipot, Springer Series in Chemical Physics, (2007) | ||
| 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) | ||
| C. Musselman, S. Pitt, K. Gulati, L. Foster, I. Andricioaei and H. Al-Hashimi, Impact of static and dynamic A-form heterogeneity on the determination of RNA global structural dynamics using NMR residual dipolar couplings, J. Biomol. NMR 36, 235-249 (2006) | ||
| C. Xing and I. Andricioaei, On the calculation of time-correlation functions by potential scaling, J. Chem. Phys. 124, 034110 (2006). | ||
| 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). | ||
| G. Luo, I. Andricioaei, X.S. Xie and M. Karplus, "Distance disorder in proteins is caused by trapping, (Letter) J. Phys. Chem. B 110, 9363-9367 (2006). | ||
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Professional Societies |
American Chemical Society American Physical Society Biophysical Society |
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| Other Experience |
Assistant Professor University of Michigan 2003—2007 |
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| Link to this profile | http://www.faculty.uci.edu/profile.cfm?faculty_id=5491 | |
| Last updated | 11/18/2009 | |
