Berkowitz Research Group

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The focus of our research is to investigate structural and dynamical
properties of biomembranes, structure and dynamics of water and
aqueous solutions at interfaces and the nature of long ranged
“hydrophobic” interactions. We use computer simulation
techniques to understand these biological and physiochemical
processes at the molecular level. We are currently working on
understanding the action of antimicrobial peptides and issues
related to understanding the nature of hydrophilic and
hydrophobic interactions.
Current projects
AMP
Surfactantcoated surfaces
Previous research
Action of antimicrobial peptides
Antimicrobial peptides (AMPs) represent a large class of small peptides that
are synthesized by organisms to protect themselves from invading pathogens.
This antimicrobial action is accomplished by inducing membrane pores
resulting in cell lysis. In our research we study the antimicrobial action of the
melittin peptide.
Nature of the problem:
Events like pore formation by AMP in membranes take place on a longer
timescale than we can simulate using a force field with atomic detail.
Therefore efficient sampling techniques are crucial to estimate
thermodynamic quantities like the free energy to understand the
mechanism of the AMP action.
A first step to understanding the mode of action of melittin is to understand
the behavior of melittin in water, on the membrane surface and in the
transmembrane orientation. A striking variation of the effect of these three
different environments is displayed in the nature of the secondary structure
of melittin.
Melittin in water, perpendicular and parallel to the membrane surface.
Qualitative analysis of the structural changes alone is not sufficient to
explain the antimicrobial action. Thermodynamic quantities like the free
energy are necessary to fully understand the mechanism of AMP action.
However the accuracy of the free energy calculations depends on the
efficiency of sampling. The potential energy surface for these systems are
complex and the system gets trapped in a local minimum close to the
starting structure. Methods like replica exchange and umbrella sampling
help improve the sampling. We currently apply these techniques to study the
free energy for the different steps in the AMP pore formation process.
Current projects
- AMP
- Surfactantcoated surfaces
Previous research
Surfactant-coated surfaces
One of the ways to prepare hydrophobic surfaces experimentally is to use
positively charged surfactants and a mica substrate. In water, the
surfactants coat the mica substrate by self-assembly and their hydrophobic
tails face water, thus making the surface (consisting of a monolayer of
surfactants) hydrophobic. The interaction between such surfactant-coated
surfaces is long-ranged and it should be distinguished from the shortrange hydrophobic interaction that has its origin in water structure next
to the surfaces.
The origin of the long-range hydrophobic interaction is still not clear, but
it was suggested that it can be due to the electrostatic interactions between
the heterogeneously charged surfaces and/or bridging effects due to
cavities. Besides, recently it was found that the nature of the interaction is
dependent on the type of surfactant counterions.
To understand the origin of these long-ranged hydrophobic interactions and
the counterion effect (or specific ion effect) on the atomistic scale, we
perform atomistic molecular dynamics (MD) simulations with a model
system composed of a sheet of mica, counterions and surfactants.
Surfactant-coated mica:
micelle (left) and
monolayer (right)
However, even with the fastest computers, studying large-size real-time
experimental systems is not possible by employing all-atom MD simulations,
since such simulations are computationally very expensive. Therefore we use
coarse-grained methodology to study certain aspects of long-range hydration
force.
1. Molecular Model of a Cell Plasma Membrane
Current projects
AMP
Surfactantcoated surfaces
Previous research
In collaboration with scientists at the Academy of Sciences of the Czech
Republic, the Berkowitz Group presented molecular dynamics
simulations of a multicomponent, asymmetric bilayer in mixed
aqueous solutions of sodium and potassium chloride. Because of the
geometry of the system, there are two aqueous solution regions in these
simulations: one mimics the intracellular region, and one mimics the
extracellular region. Ion-specific effects are evident at the
membrane/aqueous solution interface. Namely, at equal concentrations
of sodium and potassium, sodium ions are more strongly adsorbed to
carbonyl groups of the lipid headgroups.
Snapshot of a double asymmetric
membrane with separated interior
and exterior solutions.
2. Hydration Force
Recently, we have studied the interaction between phosphatidylcholine
bilayers in water, known as hydration force. To understand its origin and
molecular details, we employed a model system containing
phosphatidycholine headgroups attached to graphene plates
(PC−headgroup plates) immersed in water. The potential of mean force
(PMF) between PC−headgroup plates shows that the interaction is
repulsive and water-mediated interaction plays a major role. Furthermore,
thermodynamic analysis indicates that the attractive interaction between
polar headgroups and water molecules is responsible for the repulsion.
Two PC-headgroup plates
3. Alzheimer’s Disease Research
Certain neurodegenerative disorders represent a class of protein aggregation
diseases wherein small, misfolded proteins aggregate and lead to
deteriorating cellular function. It is imperative to understand the
mechanism by which proteins misfold and aggregate in order to develop
appropriate treatments for these disorders.
Free energy of binding of Aβ to the DPPC bilayer as a function of
Aβ-bilayer center of mass separation and number of contacts.
In Alzheimer’s disease, one of the most common of these disorders, the
Amyloid β (Aβ) peptide is the probable aggregate species. In vitro, Aβ does
not aggregate at low peptide concentrations, but the addition of model cell
membranes to a low concentration of Aβ leads to aggregation. Recently we
performed simulations that attempt to understand a possible mechanism
by which membranes influence Aβ aggregation
4. Hydrophobic Interaction and Water behavior
Hydrophobic Interaction is a multifaceted phenomenon and thus
characterizing or defining hydrophobic interaction is a challenging
problem. Along with the recent interest in water behavior in hydrophobic
interaction (dewetting phenomena), we investigated water behavior in the
confined space between hydrophobic surfaces as well as water-mediated
contribution to the free energy change (or PMF) by using simple
graphene-like “carbon” plates.
Two carbon plates in water
5. Hydrophobic Interaction between Rough Surfaces
From the contact angle measurements, it is now well-established that
molecular roughness of surfaces enhances hydrophobicity. Inspired by this
idea, we studied the effect of roughness on hydrophobic interaction. For
this study we used a model plate with rough surface. Molecular
simulations clearly demonstrated that the roughness can also enhance the
hydrophobic interaction, as well as hydrophobicity.
Water droplet on the model
rough surface
Dewetting phenomenon
between model rough surfaces
Current
Prof. Max Berkowitz
Alumni
Postdoctoral members
Jhuma Das, PhD
Changsun Eun, PhD
Sheeba Irudayam, PhD
Santo Kolattukudy Poulose, PhD
Current
Prof. Max L. Berkowitz
Alumni
Research Interests
Theoretical and Computational Chemistry and Biophysical
Chemistry
Professional Background
Ph.D., Weizmann Institute of Science (1979)
M.Sc., Novosibirsk State University (1972)
Fellow of the American Physical Society, (elected 1995)
Jhuma Das
Current
Alumni
Presently I am studying the interactions of water with surfactant covered
surfaces to understand the nature of long-ranged "hydrophobic" interactions.
To this end, we investigate surfactant-coated mica surface immersed in water
using all-atom molecular dynamics simulation. To study the hydrophobic
interactions in larger systems (several tens of nanometers) and compare our
results directly with experimental systems, we are also developing new systems
based on coarse-grain modeling approach. As a graduate student, I studied
protein, lipid and water dynamics in lipid membrane using computational and
theoretical modeling.
Research Interests
Long-ranged hydrophobic interactions in surfactant coated surfaces.
 Structure-function relationship of membrane proteins, cholesterol etc. in
biomolecular systems.
 Water at the interface of lipid bilayers, ionic interfaces and within a confined
surfaces etc.

Contact: [email protected]
Current
Changsun Eun
Alumni
As a graduate student, I studied hydrophilic and hydrophobic interactions
between nanoscale particles . Now I work on long-range hydrophobic
interaction.
Research Interests



Origin of long-range hydrophobic interaction.
Specific ion effects.
Water dynamics in a confined space and next to surfaces.
Contact: [email protected]
Current
Sheeba Irudayam
Alumni
I work on the antimicrobial peptides, evaluating the free energy for the
mechanism of action of the AMPs.
Research Interests
Understanding the structure and mechanism of action of cell membrane
components.
 Drug design.
DNA sequence processing and analysis.

Contact: [email protected]
Santo Kolattukudy Poulose
Current
Alumni
My research interests are mainly in studying biological phenomena involving
molecules such as DNA, proteins and lipids using both analytical and
computational tools. The methods used make extensive use of statistical
mechanics of polymers, chemical dynamics, field theory and coarse-grained
and molecular dynamics (MD) simulations. My current interest is in
studying equilibrium dynamics of the interaction of antimicrobial peptides
with lipid membranes.
Research Interests





Interaction of antimicrobial peptides with lipid membranes
Lipid self-assembly and phase behavior
Collective dynamics of prion proteins
Resist-developer interaction in electron beam lithography
Single chain dynamics of biomolecules
Contact: [email protected]
2010
C. Eun and M. L. Berkowitz, Fluctuations in number of water molecules confined between
nanoparticles. J. Phys. Chem. B, 114, 13410-13414 (2010).
C. H. Davis and M. L. Berkowitz, A molecular dynamics study of the early stages of amyloid- beta(142) oligomerization: The role of lipid membranes, Proteins-Structure Functions and
Bioinformatics,
78, 2533-2545 (2010).
R. Vacha, P. Jurkiewicz, M. Petrov, M. L. Berkowitz et. al., Mechanism of interaction of monovalent
ions with phosphatidylcholine lipid membranes, J. Phys. Chem. B, 114, 9504-9509 (2010).
C. Eun and M. L. Berkowitz, Thermodynamic and hydrogen-bonding analyses of the interactions
between model lipid bilayers, J. Phys. Chem. B, 114, 3013-3019 (2010).
2009
M. L. Berkowitz, Detailed Molecular Dynamics Simulations of Model Biological Membranes
Containing Cholesterol. Bioph. Bioch. Acta, 1788 86-96 (2009).
C. H. Davis and M.L. Berkowitz, Interaction between Amyloid-beta (1-42) peptide and Phospholipid
Bilayer: A Molecular Dynamics Study Biophys. J 96, 785-796 (2009).
Robert Vácha, Max L. Berkowitz, and Pavel Jungwirth, Molecular Model of a Cell Plasma
Membrane with an Asymmetric Multicomponent Composition: Water Permeation and Ion
Effects, Biophys. J. 96, 4493 - 4501 (2009)
Zhancheng Zhang and Max L. Berkowitz, Orientational Dynamics of Water in Phospholipid
Bilayers with Different Hydration Levels, J. Phys. Chem. B 113, 7676-7680 (2009)
Robert Vácha, Shirley W. I. Siu, Michal Petrov, Rainer A. Böckmann, Justyna BaruchaKraszewska, Piotr Jurkiewicz, Martin Hof, Max L. Berkowitz and Pavel Jungwirth Effects of
alkali cations and halide anions on the DOPC lipid membrane, J. Phys. Chem. A 113, 72357243 (2009)
C. Eun and M. L. Berkowitz, Origin of the hydration force: Water-mediated interaction between
two hydrophilic plates, J. Phys. Chem. B 113, 13222-13228 (2009).
C.H. Davis and M.L. Berkowitz, Structure of the Amyloid-beta (1-42) Monomer Absorbed To
Model Phospholipid Bilayers: A Molecular Dynamics Study, J. Phys. Chem. B 113, 1448014486 (2009)
Prof. Berkowitz’s office
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Caudill 017
[email protected]
Tel: 919-962-1218
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Prof. Berkowitz’s lab
Caudill 008
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Tel: 919-962-0165
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