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Dr. Ivet Bahar
Distinguished Professor & JK Vries Chair
Computational & Systems Biology Dept
School of Medicine, University of Pittsburgh
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"Bridging Structure & Function, via Dynamics"

In the News...

What we do and why:

The dynamics of living systems at the molecular level define cell survival and regulation mechanisms, which in turn, define our physiological responses. Biomolecules work together in the cell in a seamless way: they communicate (intra- and intermolecular signaling), interact with each other (chemical reactions, binding, complex formation, assembly), produce and consume energy (mitochondrial functions, metabolic events), carry cargos (ion or substrate transport). They not only sustain and regulate cell life (transcription, translation, repair), but also orderly terminate it (apoptosis). How do biomolecules achieve so many functions? Because they have flexible structures that can adapt to changes and act in specific ways (intrinsic dynamics) driven by internal or external effects, controlled by principles of physical sciences and engineering, much like synthetic materials or machines. Chemical and physical rules that apply at the microscopic scale are not any different from those of the macroscopic world. Our goal is to help improve our understanding of the basic principles of biomolecular actions with the help of computing technology, visualize/simulate their time evolution, and discover rational intervention methods to counter their dysfunction.

Student Spotlight Heading Recent Publications image Research Progress Heading

She (John) Zhang has received the Best DCSB Student Award for 2017, for his structure-based study of chromosomal dynamics using elastic network models. Below is a photo during his speech, after receiving the award, at the annual CSB Retreat Banquet.


Cihan received the Best DCSB Student Award for 2016 for his work on developing multi-scale models and simulations for dopaminergic signaling. He aims at understanding the effect of spatial complexity and heterogeneity in the efficiency of dopamine (DA) reuptake. Below is a snapshot from his simulations, displaying the release of DA (red dots) from active zones on DA neurons (green).


John received the best poster award in the DCSB retreat in June 2016 for his work on the ENM analysis of chromosome contact maps determined by Hi-C experiment.


Hongchun received the Best DCSB Postdoc Award for 2016 for developing the iGNM database and oGNM server, published in Nucleic Acids Research. The upgraded iGNM 2.0 database provides a user-friendly interface for retrieving information on the dynamics of 95% of Protein Data Bank (PDB) structures as well as their biological assemblies. It helps assess which structural elements undergo large correlated fluctuations, and enable conformational changes that may be relevant to function.



Publications 2017

Dr Ivet Bahar and co-authors Robert Jernigan and Ken Dill published a book, Protein Actions, with Garland Science.

Protein Actions

The hybrid methodology, coMD, that we have recently developed [1] has been recently extended to construct the energy landscape near the functional states of LeuT (Fig 1) [2]. This is the first energy landscape constructed for this NSS family member.

hybrid methodology

Comparative analysis of AMPAR and NMDAR dynamics reveals striking similiarities, opening the way to designing new modulators of allosteric interactions.


The work of Mary Cheng and collaborators shed light into the modulation of dopaminergic signaling by targeting human dopamine transporter (hDAT). The comparison of the effects of binding dopamine (DA), amphetamine (AMPH), orphenadrine (ORPH) (repurposable drug) and cocaine to (DAT) showed that DA or AMPH drive a structural transition towards a functional form predisposed to translocate the ligand. In contrast, ORPH inhibits DAT function by arresting it in the outward-facing open conformation. Further assays show that that ORPH, like cocaine, alters DAT uptake and endocytosis.

human dopamine transporter


"Using combined molecular modeling and experimental assay, we provide novel evidence on the molecular determinants of the dual function, substrate transport and anion permeation, of excitatory amino acid transporters (EAATs). It opens avenues toward illuminating how EAATs regulate synaptic transmission and neurological conditions. "

"IFNα2, a Type-I interferon, forms a ternary complex with two receptors, IFNAR1 and IFNAR2. The binding affinity of IFNα2 to these receptors, as well as downstream signaling strength, can be modulated by altering the dynamics of the IFNAR1. IFNα2 associated immune responses were shown to be modulated by introducing Cys-Cys double mutants which form cross-links between different subdomains of IFNAR1. This was a collaborative study with the Schreiber lab at the Weizmann Institute in Israel where experiments (binding and functional assays) have been performed."

Structural dynamics, including allosteric switches, are evolutionarily maintained to accomplish biological activities, consistent with the paradigm sequence -> structure -> dynamics -> function where 'dynamics' bridges structure and function.


"Adaptability of protein structures to enable functional interactions and evolutionary implications " Turkan Haliloglu and Ivet BaharCurrent Opinion in Structural BIology (2015) 3517-23.

"Significance of p53 dynamics in regulating apoptosis in response to ionizing radiation, and polypharmacological strategies" Liu B, Bhatt D, Oltvai ZN, Greenberger JS, Bahar ISci Rep (2014) 4:6245. PMID: 25175563

Controlling ionizing radiation (IR)-induced cell death mitigates radiation damage. Examining tumor suppressor protein p53 network dynamics in response to IR damage found that the strength of p53 transcriptional activity and its coupling (or timing with respect) to mitochondrial pore opening are major determinants of cell fate.