ANDREW T. FENLEY

E-mail: afenley@vt.edu
E-mail: afenley@ucsd.edu

Research papers by Andrew Fenley
Profile on Google Scholar

POSTDOC

University of California San Diego, San Diego, CA
Professor Michael K. Gilson's Group
Skaggs School of Pharmacy and Pharmaceutical Sciences
August 2nd, 2010 - Present

EDUCATION

Virginia Tech, Blacksburg, VA
B.S., Physics, Minors in Math and Chemistry, Spring 2003
M.S., Physics, Spring 2007
Ph.D., Physics, July 2nd 2010

GRADUATE ADVISORS

Professor Rahul Kulkarni, Department of Physics
Professor Alexey Onufriev, Department of Computer Science

AWARDS

April 2009: Clayton D. Williams Graduate Fellowship in Theoretical Physics

July 2006 - July 2009: EIGER FELLOW (NSF IGERT)

DISSERTATION RESEARCH

"GEM" -- Analytical Poisson-Boltzmann


Many important interactions at the molecular level are directed by electrostatic forces. Since the introduction of atomic resolution structures from X-ray crystallography and the foundation of the Protein DataBank, a plethora of computation tools have been produced to analyze these freely available structures. One aspect of my research focuses on determining the electrostatic potential at and near the surface of large biomolecules. The potential can then be used to find electrostatic regions of interest across the surface that might be involved with the function of the biomolecule. Recently (in collaboration with Wu-chun Feng's group), we've sped up our analytical tools through the use of graphical processing units (GPUs).


(LEFT) A picture of the electrostatic potential in the active pocket of the protein lysozyme . The picture also serves as a link to download the "GEM" software package used to calculate the surface potentials.

(RIGHT) A picture of a the electrostatic potential of a viral capsid which is nearly half a million atoms in size. The calculation was sped up by 2300 fold using GPUs. The picture links to a recent article in Scientific American discussing the work.


Nucleosome Stability


Eukaryotes store their DNA inside a nucleus, which is about one micron in diameter. However, the DNA itself can stretch to over a meter in length depending on the organism. The high level of compaction the DNA must undergo to fit inside the nucleus is critical for the cell. The first level of compaction consists of the DNA repeatedly wrapping a couple of times around beads of proteins called histones. The result looks like a string of pearls, where the pearls are called Nucleosomes (histones with wrapped DNA) and the string connecting the Nucleosomes are unwrapped DNA. Understanding how the DNA wraps and unwraps from the histones is important for studying the transcription of certain genes, for example those genes whose RNA polymerase binding sites would be occluded when wrapped around the histones. My research involves modeling the stability of the Nucleosome relative to changes in the system, where the changes are electrostatic in nature -- salt concentrations, total charge of the histones, etc.


3D Structure of the Nucleosome


Quorum Sensing


Certain bacteria are able to orchestrate the starting and stopping of critical functions depending on the size of the bacterial colony. These bacteria are known as quorum sensing bacteria. The bacteria are constantly producing, secreting, and detecting small signaling molecules called autoinducers. When the concentration of autoinducers reaches a critical amount, the cells in the colony turn on a particular function, for example the bacteria will produce light. My research involves modeling all the different interactions inside the cell corresponding to the quorum sensing regulatory network and then combining the insights gained from the model with experimental data. In particular, I look at how small RNA regulation (the interaction between messenger RNA and small segments of complimentary RNA) plays a significant role in the quorum sensing pathway. Both mean-field and stochastic approaches are considered in my work.




PUBLICATIONS

13.) Andrew T. Fenley, Hari S. Muddana, and Michael K. Gilson - Entropy-enthalpy transduction due to conformational shifts can obscure the forces driving protein-ligand binding, Proceedings of the National Academy of Sciences USA., 109(49), 20006-20011 (2012).

12.) Abhishek Mukhopadhyay*, Andrew T. Fenley*, Igor S. Tolokh*, and Alexey V. Onufriev - Charge Hydration Asymmetry: The Basic Principle and How to Use It to Test and Improve Water Models, Journal of Physical Chemistry B., 116(32), 9776-9783 (2012). F1000 Article

11.) Alban R. Pereira, Andrew J. Kale, Andrew T. Fenley, Tara Byrum, Hosana M. Debonsi, Michael K. Gilson, Frederick A. Valeriote, Bradley S. Moore, William H. Gerwick - The Carmaphycins: New Proteasome Inhibitors Exhibiting an α, β‐Epoxyketone Warhead from a Marine Cyanobacterium, ChemBioChem, 13(6), 810-817 (2012).

10.) Vlad Elgart, Tao Jia, Andrew T. Fenley and Rahul Kulkarni - Connecting protein and mRNA burst distributions for stochastic models of gene expression, Physical Biology, 9, (2011) 046001.

9.) Andrew T. Fenley, Suman K. Banik, and Rahul V. Kulkarni - Computational modeling of differences in the quorum sensing induced luminescence phenotypes of Vibrio harveyi and Vibrio cholerae, Journal of Theoretical Biology, 274(1), 145-153 (2011).

8.) Andrew T. Fenley, David A. Adams, and Alexey V. Onufriev - Charge state of the globular histone core controls stability of the nucleosome, Biophysical Journal, 99(5), 1577-1585 (2010).

7.) Ramu Anandakrishnan, Tom R. W. Scogland, Andrew T. Fenley, John C. Gordon, Wu-chun Feng, and Alexey V. Onufriev - Accelerating electrostatic surface potential calculation with multi-scale approximation on graphics processing units, Journal of Molecular Graphics and Modelling, 28(8), 904-910 (2010).

6.) Suman K. Banik*, Andrew T. Fenley*, and Rahul V. Kulkarni - A model for signal transduction during quorum sensing in Vibrio harveyi, Physical Biology, 6(4), 046008 (2009).

5.) A. Navid, C.-M. Ghim, A.T. Fenley, S. Yoon, S. Lee, E. Almaas - Chapter: Systems biology of microbial communities, Systems Biology - Methods of Molecular Biology Series, Maly, Ivan V. (Ed.), Vol. 500, XII, 500 p. 138 illus., Hardcover. ISBN: 978-1-934115-64-0 (2009).

4.) G. Sigalov, A. Fenley, P. Scheffel, and A. Onufriev - Analytical linearized Poisson-Boltzmann model of biomolecular solvation - in Proc. of International conference on Non-linear Phenomena in Polymer Solids and Low-dimensional Systems, Moscow, Russia, July 7-10 (12 pages) (2008).

3.) Andrew T. Fenley, John C. Gordon, and A. Onufriev - An Analytical Approach to Computing Biomolecular Electrostatic Potential, I: Derivation and Analysis, Journal of Chemical Physics, 129(7), 075101 (2008).

2.) John C. Gordon, Andrew T. Fenley, and A. Onufriev - An Analytical Approach to Computing Biomolecular Electrostatic Potential, II: Validation and Applications, Journal of Chemical Physics, 129(7), 075102 (2008).

1.) Grigori Sigalov, Andrew Fenley, and Alexey Onufriev - Analytical electrostatics for biomolecules: Beyond the generalized Born approximation, Journal of Chemical Physics, 124(12), 124902 (2006).

* Contributed equally

SEMINAR TALKS

Fall 2009 Condensed Matter Seminars (Nov. 16th): Talk Entitled - Biophysical modeling of quorum sensing and the stability of the nucleosome.

CONFERENCES

2012 ACS Meeting in San Diego, CA: Poster Entitled - .

2012 Biophysical Meeting in San Diego, CA: Poster Entitled - .

2009 APS March Meeting in Pittsburgh, PA, March 16-20 2009: Talk Entitled - An Analytical Approach to Computing Biomolecular Electrostatic Potential.

2008 Gordon Research Conference - Computational Chemistry, July 27th - August 1st, 2008: Poster Entitled - Physics-Based Analytical Biomolecular Electrostatics.

2008 Gordon Research Conference - Biopolymers, June 8-13, 2008: Poster Entitled - Electrostatic Analysis of The Nucleosome Stability.

2007 ASM Conference on Cell-Cell Communication, October 7-10, 2007: Poster Entitled - Computational modeling of small RNA-based regulation during quorum sensing in Vibrio harveyi and Vibrio cholerae.

2007 Gordon Research Conference - Nucleic Acids, June 3-8, 2007: Poster Entitled - Electrostatic Analysis of The Nucleosome Stability.

2007 APS March Meeting in Denver, Colorado, March 5-9, 2007: Talk Entitled - Modeling the dynamics of the nucleosome at various levels, Poster Entitled - Electrostatic Analysis of The Nucleosome Stability, Poster Entitled - Computational modeling of the quorum-sensing network in bacteria.

36th Mid-Atlantic Macromolecular Crystallography Meeting at Wake Forest University, June 2nd 2006: Poster Entitled - Analytical solutions of the Poisson-Boltzmann equation: biological applications

Virginia Tech Structural Biology Symposium at Virginia Tech, March 31st, 2006: Poster Entitled - Analytical solutions of the Poisson-Boltzmann equation: biological applications

231st ACS National Meeting in Atlanta, Georgia, March 26-30, 2006: Poster Entitled - Analytical solutions of the Poisson-Boltzmann equation: biological applications

2006 APS March Meeting in Baltimore, Maryland, March 13-17, 2006: Poster Entitled - Analytical solutions of the Poisson-Boltzmann equation: biological applications, Talk Entitled - Modeling of signal transduction in bacterial quorum-sensing.

Mathematics as an Enabling Science at Virginia Tech, September 30 - October 2, 2005: Talk Entitled - Analytical solutions of the Poisson-Boltzmann equation: biological applications

Coding Theory and Quantum Computing Conference at the University of Virginia, May 20-24, 2003