Research

Multi-scale Modeling of Viral Infection

I, together with our Team, investigating various aspects of viral infection process, such as capsid disassembly and transport. Using an intertwined theoretical/computational and experimental approach gives us unique opportunities to explore different size and time scales: from atomistic level-micro-seconds resolution to whole-cell-hour scale.

Key publication: Z. Ghaemi (corresponding author) and M. Gruebele, A Spatial Whole-Cell Model for HBV Viral Infection and Drug Interactions, bioRxiv, Submitted, 2022

Z. Ghaemi, M. Gruebele and E. Tajkhorshid Molecular mechanisms of virus capsid disassembly, Proc Nat Acad Sci,118, e2102530118, 2021, Featured in UIUC News, Phys.org, EurekAlert, Technology Networks, SCIEMAG, Florida News Times

Computational Human Whole-Cell Platform

I have developed the first computational human cell model with spatial resolution, in addition to kinetic models of the accuracy needed for describing RNA splicing processing. After simulating this model for 15 minutes of biological time, I could reveal how spliceosomal assembly is influenced by cell-to-cell heterogeneities and stochasticities in the abundance of spliceosome components. The human cell model is an adaptable platform for studying other important biological processes and is openly available through Github.

Key publication: Z. Ghaemi, J. Peterson, M. Gruebele and Z. Luthey-Schulten

An in-silico mammalian whole-cell model reveals the influence of spatial organization on RNA splicing efficiency, PLoS Comput Biol, 16(3): e1007717, 2020

Featured in UIUC News, Phys.org, EurekAlert

Thermodynamics & Kinetics of Protein-RNA Complexes

Typically, the calculation of binding affinity requires long molecular dynamics or enhanced sampling simulations, which may not always be feasible for large systems. I developed a method that utilizes structural correlations within the protein-RNA complex, for estimating binding affinities. The method is fast and one that yields binding affinities close to the measured values with relatively short simulations.

Key publications: G. Gopan*, Z. Ghaemi*, C. Davis, and M. Gruebele
Spliceosomal SL1 RNA binding to U1-70K: the role of the extended RRM, Nucleic Acids Res, In press, 2022.

Z. Ghaemi, I. Guzman, Z. Luthey-Schulten and M. Gruebele,

Role of Electrostatics in Protein–RNA Binding: The Global vs the Local Energy Landscape, J Phys Chem B, 121, 8437-8446, 2017

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Z. Ghaemi, I. Guzman, J. Baek, M. Gruebele and Z. Luthey-Schulten,

Estimation of relative protein–RNA binding strengths from fluctuations in the bound state, J Chem Theory Comp, 12, 4593–4599, 2016

Mechanisms of drug molecules membrane transport

For drug-like molecules, it is necessary to explicitly consider chemical aspects of the molecule that are relevant for permeation. I took the approach of describing permeation as a multi-dimensional process, and developed a theoretical framework to combine pieces together and get the permeability coefficient estimate. The permeability coefficients of a small molecule and two anti-HIV drugs were estimated using this method.

Key publications: Z. Ghaemi, M. Minozzi, P. Carloni and A. Laio,

A novel approach to the investigation of passive molecular permeation through lipid bilayers from atomistic simulation, J Phys Chem B, 116, 8714-8721, 2012. Featured on cover

Z. Ghaemi, D. Alberga, P. Carloni, A. Laio and G. Lattanzi,

Predicting the permeability coefficient of pharmacologically relevant molecules using atomistic simulations, J Chem Theory Comp, 12, 4093–4099, 2016