Participant: PROMISE AGEP Research Symposium
Department: Chemical and Biomolecular Engineering, A. James Clark School of Engineering
Institution: University of Maryland, College Park
PROMISE AGEP Research Symposium 2015
Binding of a curvature-sensing peptide in yeast, a molecular dynamics study
This work summarizes preliminary results in the study of a peripheral membrane protein’s (Osh4) binding mechanism. This protein is member of a family of seven homologue oxysterol binding proteins in yeast, and has six membrane binding regions (JMB 2012, 423:847-862). Nonspecific interactions with anionic lipids are an important driving force for the Osh4 attraction to membranes. The ALPS-like motif of Osh4, a 29 amino acid peptide that forms the lid to protect sterols, has been identified as a membrane curvature sensor that binds to membranes with surface-packing defects (NSMB 2007, 14(2):138-146; BJ 2013, 104:575-584). Initial results gave us insight on the binding mechanism of the peptide with charged and neutral bilayers containing different lipid types. Unsaturated lipids and increasing values of surface tension (γ) were implemented to increase the surface packing defects of our membrane models. The simplest model had only phosphatidylcholine (PC) lipids; phosphatidylserine (PS) and ergosterol (ERG) were added to model yeast membranes more closely. Finally, two complex yeast membrane models with phosphoinositol (PI) lipids (anionic) were also studied. Short simulations runs were done in triplicates, 200ns each, for pure (neutral) DOPC bilayers. The charged membranes were run on the Anton machine for 2µs per replicate run. Binding events were characterized through hydrogen bonding and binding energy calculations, finding SER8, ALA5, TYR4, and LYS15 as recurrent binding residues.
PROMISE AGEP Research Symposium 2014
Molecular Dynamic Simulations of Organelle-Specific Yeast Membrane Models
The present study analyzes improved computational membrane models for specific organelles in yeast. Previous molecular dynamic (MD) simulations were performed on yeast membrane models having six lipid types with lipid composition averages between the endoplasmic reticulum (ER) and the plasma membrane (PM) (BJ. 97:50-58). The models studied in this research include ergosterol (ERG), phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI) lipids, with bilayer diversity ranging between six and eleven lipid types. MD simulations were used to equilibrate systems with lipid compositions characteristic to the ER, PM, and Golgi network (TGN) membranes based on experimental data (Yeast 15:1555-1564; Yeast 15: 601-614; JCB 146:741-754; JCB 185:601-612; ). Data analysis provided better understanding of membrane behavior, mechanical properties, order parameters, electron density profiles (EDPs), and lipid packing – the calculated properties follow expected trends. Selected models will be used to advance the study of peripheral membrane Osh4 binding mechanism and function.
I grew up in La Paz, Bolivia, and moved to the United States eight years ago after I finished high school. I enrolled in Chemical Engineering at Montgomery College, and transfer to the University of Maryland (UMD) to complete my degree. I volunteered as an undergraduate at my advisor’s lab doing molecular simulations, and decided to stay to pursue my MS and PhD degrees. I completed my MS degree December 2014, and have been blessed to participate presenting my work in several local, national, and international conferences or symposia. My research is focused on computational simulations of biological systems based on thermodynamic laws. My career goal is to become a university professor to form and help students as they choose their career paths. To meet this goal I have been involved in TA experiences and recently join the OXE Chemical Engineering Honor Society, which offers tutoring services to students on campus. I hope to join the Future Faculty Program at the A. James Clark School of Engineering later this year to get a more hands-on experience in teaching. As a professor, I would like to establish collaboration programs with scientists in Latin-America to motivate the development of science in my home country Bolivia. I am thankful for my advisor’s and the LSAMP community at UMD for their financial and moral support that helped me get this far in my professional degree. Outside of school I am an active youth leader at my local Seventh Day Adventist Church, and enjoy doing crafts.
GENERAL SUMMARY OF GRADUATE RESEARCH
I continued my graduate studies at UMD under my undergraduate advisor’s mentoring. My research has focused on the study of physical properties of yeast membrane models, and the influence on sterol content on these properties. The membrane models were, afterwards, used to study the biding mechanism and function of peripheral membrane proteins, such as the oxysterol-binding protein homologue (Osh-) family in yeast cells. I presented the yeast models work at the AIChE national meeting on November 2013, and expand the calculations to present them at the Biophysical meeting on February 2014. Part of the studies leading to my PhD work includes a small peptide (ALPS-like motif) of the peripheral protein Osh4 in yeast. The function of this protein is not yet well understood, learning more about the small peptide binding mechanism gave us more insight about the entire protein interaction with membrane bilayers. I had the opportunity to present preliminary results at the Congress of Theoretical Chemists of Latin Expression (QUITEL) on November 2014, held at the Galapagos Islands, Ecuador. The software packages used in my research are CHARMM, NAMD, and VMD. I have also been involved in smaller projects with undergraduate students in the lab, and collaborating with Dr. Im’s Lab at the University of Kansas on a project to facilitate building and analysis of simulation data – we have published two articles as results of our work (JCC 2014, 35(27):1997-2004; JCC 2014, 35(12):957-963). Computational resources from the High-Performance Computing Cluster (HPCC) at UMD, Kraken and Stampede at XSEDE (NSF grants), and time at the ANTON machine enable my research.
SELECTED LIST OF PRESENTATIONS AND PUBLICATIONS
- Wu, E.L.; Cheng, X.; Jo, S.; Rui, H.; Song, K.C.; Davila-Contreras, E.M.; Qi, Y.; Lee, J.; Monje-Galvan, V.; Venable, R.M.; Klauda, J.B.; Im, W. 2014. CHARMM_GUI Membrane Builder toward Realistic Biological Membrane Simulations. Comput. Chem. 35(27), 1997-2004. DOI: 10.1002/jcc.23702
- Jeong, J.C.; Jo, S.; Wu, E.L.; Qi, Y.; Monje-Galvan, V.; Yeom, M.S.; Gorenstein, L.; Chen, F.; Klauda, J.B.; Im, W. 2014. ST-Analyzer: A web-based user interface for simulation trajectory analysis. Comput. Chem. 35(12), 957-963. DOI: 10.1002/jcc.23584
- Klauda, J.B.; Monje, V.; Kim, T.; Im, W. 2012. Improving the CHARM Force Field for Polyunsaturated Fatty Acid Chains. Phys. Chem. B. 116(31), 9424-9431.
- XL Congress of Theoretical Chemists of the Latin Expression QUITEL 2014 (talk in Spanish). Galapagos, Ecuador; November 2014. Membrane binding of a curvature-sensing peptide of a lipid transport protein in yeast. Viviana Monje-Galvan, Jeffery B. Klauda. ISBN: 978-9978-68-070-4 (p.19)
- 58th Biophysical Society National Meeting (poster session). San Francisco, CA 2014. Molecular dynamic studies on organelle-specific yeast membrane models and amphipathic lipid packing sensor motif binding mechanism. Viviana Monje-Galvan, Jeffery B. Klauda. DOI: 1016/j.bpj.2013.11.3916
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