Protein memory(seminar report)

PROTEIN BASED MEMORY STORAGE DEVICES 1

1. INTRODUCTION

Since the dawn of time, man has tried to record important events and techniques
for everyday life. At first, it was sufficient to paint on the family cave wall how one
hunted. Then came people who invented spoken languages and the need arose to record
what one was saying without hearing it firsthand. Therefore, years later, earlier scholars
invented writing to convey what was being said. Pictures gave way to letters which
represented spoken sounds. Eventually clay tablets gave way to parchment, which gave
way to paper. Paper was, and still is, the main way people convey information.

However, in the mid twentieth century computers began to come into general use.
Computers have gone through their own evolution in storage media. In the forties, fifties,
and sixties, everyone who took a computer course used punched cards to give the
computer information and store data. In 1956, researchers at IBM developed the first disk
storage system. This was called RAMAC (Random Access Method of Accounting and
Control).

Since the days of punch cards, computer manufacturers have strived to squeeze
more data into smaller spaces. That mission has produced both competing and
complementary data storage technology including electronic circuits, magnetic media like
hard disks and tape, and optical media such as compact disks. Today, companies
constantly push the limits of these technologies to improve their speed, reliability, and
throughput -- all while reducing cost. The fastest and most expensive storage technology
today is based on electronic storage in a circuit such as a solid state "disk drive" or flash
RAM. This technology is getting faster and is able to store more information thanks to
improved circuit manufacturing techniques that shrink the sizes of the chip features. Plans
are underway for putting up to a gigabyte of data onto a single chip.

Department of Electronics and Communication, LMCST


Magnetic storage technologies used for most computer hard disks are the most
common and provide the best value for fast access to a large storage space. At the low
end, disk drives cost as little as 25 cents per and provide access time to data in ten
milliseconds. Drives can be ganged to improve reliability or throughput in a Redundant
Array of Inexpensive Disks (RAID). Magnetic tape is somewhat slower than disk, but it is
significantly cheaper per megabyte. At the high end, manufacturers are starting to ship
tapes that hold 40 gigabytes of data. These can be arrayed together into a Redundant Array
of Inexpensive Tapes (RAIT), if the throughput needs to be increased beyond the
capability of one drive. For randomly accessible removable storage; manufacturers are
beginning to ship low-cost cartridges that combine the speed and random access of a hard
drive with the low cost of tape. These drives can store from 100 megabytes to more than
one gigabyte per cartridge.

Standard compact disks are also gaining a reputation as an incredibly cheap way of
delivering data to desktops. They are the cheapest distribution medium around when
purchased in large quantities ($1 per 650 megabyte disk). This explains why so much
software is sold on CD-ROM today. With desktop CD-ROM recorders, individuals are
able to publish their own CD-ROMs.

With existing methods fast approaching their limits, it is no wonder that a number
of new storage technologies are developing. Currently, researches are looking at protein-
based memory to compete with the speed of electronic memory, the reliability of magnetic
hard-disks, and the capacities of optical/magnetic storage. We contend that three-
dimensional optical memory devices made from bacteriorhodopsin utilizing the two
photon read and write-method is such a technology with which the future of memory lies.



2. PRESENT MEMORY STORAGE DEVICES

The demands made upon computers and computing devices are increasing each
year, speeds are increasing at an extremely fast clip. However, the RAM used in most
computers is the same type of memory used several years ago. The limits of making
RAM denser are being reached. Surprisingly, these limits may be economical rather
than physical. A decrease by a factor of two in size will increase the cost of
manufacturing of semiconductor pieces by a factor of 5.

Currently, RAM is available in modules called DIMMs and SIMMs .These
modules can be bought in various capacities from a few hundred kilobytes of RAM to
about 64 megabytes. Anything more is both expensive and rare. These modules are
generally 70ns; however 60ns and 100ns modules are available. The lower the
nanosecond rating, the more the module will cost. Currently, a 64MB DIMM costs over
$400. All DIMMs are 12cm by 3cm by 1cm or about 36 cubic centimeters. Whereas a 5
cubic centimeter block of bacteriorhodopsin studded polymer could theoretically store
512 gigabytes of information. When this comparison is made, the advantage becomes
quite clear. Also, these bacteriorhodopsin modules could also theoretically run 1000
times faster.

In response to the demand for faster, more compact, and more affordable
memory storage devices, several alternatives have appeared in recent years. Among the
most promising approaches include memory storage using protein-based memory.



3. PROTEIN-BASED MEMORY

There have been many methods and proteins researched for use in computer
applications in recent years. However, among the most promising approaches, the
main one is 3-Dimensional Optical RAM storage using the light sensitive protein
bacteriorhodopsin.

Bacteriorhodopsin is a protein found in the purple membranes of several species
of bacteria, most notably Halobacterium halobium. This particular bacterium lives in
salt marshes. Salt marshes have very high salinity and temperatures can reach 140
degrees Fahrenheit. Unlike most proteins, bacteriorhodopsin does not break down at
these high temperatures.

Early research in the field of protein-based memories yielded some serious
problems with using proteins for practical computer applications. Among the most
serious of the problems was the instability and unreliable nature of proteins, which are
subject to thermal and photochemical degradation, making room-temperature or higher-
temperature use impossible. Largely through trial and error, and thanks in part to
nature's own natural selection process, scientists stumbled upon a light-harvesting
protein that has certain properties which make it a prime candidate for computer
applications. While bacteriorhodopsin can be used in any number of schemes to store
memory, we will focus our attention on the use of bacteriorhodopsin in 3-Dimensional
Optical Memories.



4. DEVELOPMENT IN THE FIELD OF MOLECULAR
ELECTRONICS

There is a revolution fomenting in the semiconductor industry. It may take 30
years or more to reach perfection, but when it does the advance may be so great that
today's computers will be little more than calculators compared to what will come after.
The revolution is called molecular electronics, and its goal is to depose silicon as king
of the computer chip and put carbon in its place. The perpetrators are a few clever
chemists trying to use pigment, proteins, polymers, and other organic molecules to
carry out the same task that microscopic patterns of silicon and metal do now.

For years these researchers worked in secret, mainly at their blackboards,
plotting and planning. Now they are beginning to conduct small forays in the
laboratory, and their few successes to date lead them to believe they were on the right
track. "We have a long way to go before carbon-based electronics replace silicon-based
electronics, but we can see now that we hope to revolutionize computer design and
performance," said Robert R. Birge, a professor of chemistry, Carnegie-Mellon
University, Pittsburgh. "Now it's only a matter of time, hard work, and some luck
before molecular electronics start having a noticeable impact." Molecular electronics is
so named because it uses molecules to act as the "wires" and "switches" of computer
chips. Wires may someday be replaced by polymers that conduct electricity, such as
polyacetylene and polyphenylenesulphide. Another candidate might be organometallic
compounds such as porphyrins and pthalocyanines which also conduct electricity.
When crystallized, these flat molecules stack like pancakes, and metal ions in their
centers line up with one another to form a one-dimensional wire.

Many organic molecules can exist in two distinct stable states that differ in some
measurable property and are interconvertable.These could be switches of molecular
electronics. For example, bacteriorhodopsin, a bacterial pigment, exists in two optical
states: one state absorbs green light, the other orange. Shinning green light on the
green-absorbing state converts it into the orange state and vice versa. Birge and his
coworkers have developed high density memory drives using bacteriorhodopsin.



"Electron transport in photosynthesis one of the most important energy generating
systems in nature, is a real-world example of what we're trying to do," said Phil Seiden,
manager of molecular science, IBM, Yorkstown Heights, N.Y. Birge, who heads the
Center for Molecular Electronics at Carnegie-Mellon, said two factors are driving this
developing revolution, more speed and less space.

"Semiconductor chip designers are always trying to cram more electronic
components into a smaller space, mostly to make computers faster," he said. "And
they've been quite good at it so far, but they are going to run into trouble quite soon." A
few years ago, for example, engineers at IBM made history last year when they built a
memory chip with enough transistors to store a million bytes if information, the
megabyte. It came as no big surprise. Nor did it when they came out with a 16-megabyte
chip.

Chip designers have been cramming more transistors into less space since Jack
Kilby at Texas Instruments and Robert Noyce at Fairchild Semiconductor first showed
how to put multitudes on electronic components on a slab of silicon. But 16 megabytes
may be near the end of the road. As bits get smaller and loser together, "crosstalk"
between them tends to degrade their performance. If the components were pushed any
closer they would short circuit. Physical limits have triumphed over engineering. That is
when chemistry will have its day. Carbon, the element common to all forms of life, will
become the element of computers too. "That is when we see electronics based on
inorganic semiconductors, namely silicon and gallium arsenide, giving way to
electronics based on organic compounds," said Scott E. Rickert, associate professor of
macromolecular science, Case Western Reserve University, Cleveland, and head of the
school's Polymer Micro device Laboratory. "As a result," added Rickert, "we could see
memory chips store billions of bytes of information and computers that are thousands
times faster. The science of molecular electronics could revolutionize computer design."



5. WHY BACTERIORHODOPSIN?

Bacteriorhodopsin (BR), a photon-driven proton pump, is a transmebrane
protein found in the purple membrane of the archaeon, Halobacterium halobium. The
BR is organized with polyprenoid lipid chains in the hydrophobic moiety on a highly
ordered two-dimensional lattice in the membrane. Enormous interest has been
generated by application of the structural and dynamic properties of the BR protein in
bioelectronics devices. Embedding bacteriorhodopsin in membrane films is essential to
achieve functionality of such devices. Although some prototype devices have been
fabricated, instability of the membranes is acknowledged as a major impediment to the
development of BR-based devices. Whereas there has been much biotechnological
experimentation on the properties and functionalities of the BR protein, comparatively
little attention has been paid to the critically important supporting lipid matrices in
which BR functions. Archaeal membranes consist predominantly of isoprenoid chains
ether-linked to an alcohol such as glycerol. These isoprene structures are unique and are
not prone to decomposition at high temperatures. That isoprene molecular fossils have
been found in geologic Miocene deposits attests to the extreme durability and stability
of these structures. In viable organisms BR functions in high efficiency at temperatures
as high as 140˚C, in near-saturating concentrations of salt, and in highly acidic
environments. Specific lipids of the purple membrane are required for normal
bacteriorhodopsin structure, function, and photo cycle kinetics.At ambient
temperatures,the membranes are in a liquid crystalline state that provides optimal
functioning of the BR..Adaptations of the membrane lipids allow maintenance of the
liquid crystalline state even as the indigenous conditions change. Nevertheless, as a
consequence of light absorption, BR initiates a photo cycle through structurally
distinctive conformations, causing tractable optical and electronic properties of the
protein. The characteristics of the lipids in the membrane dictate the large-amplitude
motions of BR,and by consequence the broad utility of bR in bioelectronic devices.The
research to be developed under this topic would have military and civilian importance.
Some of the bionanotechnological applications that are anticipated include: ultra rapid
optical data acquisition with parallel processing capabilities and extreme high density
holographic 3-dimensional data and image storage.



6. BACTERIORHODOPSIN OPTICAL MEMORY

Following are the features of Bacteriorhodopsin Optical Memory:-

1. Purple membrane from Halobacterium Halobium

2. Bistable red/green switch

3. In protein coat at 77K, 107-108 cycles

4.10,000 molecules/bit

5. Switching time, 500 femtoseconds

6. Monolayer fabricated by self-assembly

7. Speed currently limited by laser addressing

Using the purple membrane from the bacterium Halobacterium Halobium, Prof.
Robert Birge and his group at Syracuse University have made a working optical
bistable switch, fabricated in a monolayer by self-assembly, that reliably stores data
with 10,000 molecules per bit. The molecule switches in 500 femtoseconds--that's
1/2000 of a nanosecond, and the actual speed of the memory is currently limited by
how fast you can steer a laser beam to the correct spot on the memory.



6.1 THE STRUCTURE OF BACTERIORHODOPSIN

Bacteriorhodopsin - as all retinal proteins from Halo bacterium - folds into a
seven-Tran membrane helix topology with short interconnecting loops. The helices
(named A-G) are arranged in an arc-like structure and tightly surround a retinal
molecule that is covalently bound via a Schiff base to a conserved lysine (Lys-216) on
helix G. The cross-section of BR with residues important for proton transfer and the
probable path of the proton are shown in Fig.1. The 3D structure is also available.
Retinal separates a cytoplasmic from an extra cellular half channel that is lined by
amino acids crucial for efficient proton transport by BR . The Schiff base between
retinal and Lys-216 is located at the center of this channel. To allow vectorial proton
transport, de- and reprotonation of the Schiff base must occur from different sides of
the membrane. Thus, the accessibility of the Schiff base for Asp-96 and Asp-85 must
be switched during the catalytic cycle. The geometry of the retinal, the protonation state
of the Schiff base, and its precise electrostatic interaction with the surrounding charges
and dipoles tune the absorption maximum to fit its biological function.

Fig. 1: The 3D structure of Bacteriorhodopsin



6.2 BACTERIORHODOPSIN PHOTOCYCLE

Fig 2:Bacteriorhopsin Photocycle

Bacteriorhodopsin comprises of a light absorbing component known as
CHROMOPHORE that absorbs light energy and triggers a series of complex internal
structural changes to alter the protein’s optical and electrical characteristics. This
phenomenon is known as photocycle. In response to light Bacteriorhodopsin “pumps”
proton across the membrane, transporting charged ions in and out of the cell.
Bacteriorhodopsin goes through different intermediates during the proton pumping
cycle. These stages have been labelled K, L, M, N and O, each one easily identifiable
because Bacteriorhodopsin changes colour during each stage of the process. The native
photo cycle has several spectroscopically unique steps, bR --> K <--> L <--> M1
-->M2 <--> N <-->O, which occur in a roughly linear order The photo cycle of
bacteriorhodopsin or its cycle of molecular states depend on the luminous radiation that
it absorbs. The initial state known as bR evolves into state K under the effect of green
light. From there it spontaneously passes to state M then to state O (relaxation
transitions).



Exposure to red light from O state will make the structure of the bacterium
evolve to state P then spontaneously to state Q, which is a very stable state.

Some of the intermediates are stable at about 80K and some are stable at room
temperature, lending themselves to different types of RAM. Nevertheless, radiation
from blue light can take the molecule from state Q back to the initial state bR. Any two
long lasting states can be assigned the binary value 0 or 1, making it possible to store
information as a series of Bacteriorhodopsin molecules in one state or another.
Genetic engineering has been used to create bacteriorhodopsin mutants with enhanced
materials properties.

Three-dimensional optical memory storage offers significant promise for the
development of a new generation of ultra-high density RAMs. One of the keys to this
process lies in the ability of the protein to occupy and form cubic matrices in a polymer
gel, allowing for truly three-dimensional memory storage. The other major component
in the process lies in the use of photons to read and write data. As discussed earlier,
storage capacity in two-dimensional optical memories is limited to approximately
1/lambda2 (lambda = wavelength of light), which comes out to approximately 108 bits
per square centimeter. Three-dimensional memories, however, can store data at
approximately 1/lambda3, which yields densities of 1011 to 1013 bits per cubic
centimeter. The memory storage scheme which we will focus on, proposed by Robert
Birge in Computer (Nov. 1992), is designed to store up to 18 gigabytes within a data
storage system with dimensions of 1.6 cm * 1.6 cm * 2 cm. Bear in mind, this memory
capacity is well below the theoretical maximum limit of 512 gigabytes for the same
volume (5-cm3).



6.3 DATA WRITING TECHNIQUE

Bacteriorhodopsin, after being initially exposed to light (in our case a laser
beam), will change to between photo isomers during the main photochemical event
when it absorbs energy from a second laser beam. This process is known as sequential
one-photon architecture, or two-photon absorption. While early efforts to make use of
this property were carried out at cryogenic temperatures (liquid nitrogen
temperatures), modern research has made use of the different states of
bacteriorhodopsin to carry out these operations at room-temperature.

Fig 3. Data Writing Technique

The process breaks down like this:

Upon initially being struck with light (a laser beam), the bacteriorhodopsin
alters its structure from the bR native state to a form we will call the O state. After a
second pulse of light, the O state then changes to a P form, which quickly reverts to a
very stable Q state, which is stable for long periods of time (even up to several years).



The data writing technique proposed by Dr. Birge involves the use of a three
dimensional data storage system. In this case, a cube of bacteriorhodopsin in a
polymer gel is surrounded by two arrays of laser beams placed at 90 degree angles
from each other. One array of lasers, all set to green (called "paging" beams), activates
the photo cycle of the protein in any selected square plane, or page, within the cube.
After a few milliseconds, the number of intermediate O stages of bacteriorhodopsin
reaches near maximum. Now the other set, or array, of lasers - this time of red beams -
is fired.

The second array is programmed to strike only the region of the activated
square where the data bits are to be written, switching molecules there to
the P structure. The P intermediate then quickly relaxes to the highly stable Q state.
We then assign the initially-excited state, the O state, to a binary value of 0, and the P
and Q states are assigned a binary value of 1. This process is now analogous to the
binary switching system which is used in existing semiconductor and magnetic
memories. However, because the laser array can activate molecules in various places
throughout the selected page or plane, multiple data locations (known as "addresses")
can be written simultaneously - or in other words, in parallel.

6.4 DATA READING TECHNIQUE

The system for reading stored memory, either during processing or extraction
of a result relies on the selective absorption of red light by the O intermediate state of
bacteriorhodopsin. To read multiple bits of data in parallel, we start just as we do in
the writing process. First, the green paging beam is fired at the square of protein to be
read. After two milliseconds (enough time for the maximum amount of O
intermediates to appear), the entire red laser array is turned on at a very low intensity
of red light. The molecules that are in the binary state 1 (P or Q intermediate states)
do not absorb the red light, or change their states, as they have already been excited
by the intense red light during the data writing stage.



Fig 4.Data Reading Technique

However, the molecules which started out in the binary state 0 (the O
intermediate state), do absorb the low-intensity red beams. A detector then images
(reads) the light passing through the cube of memory and records the location of the
O and P or Q structures; or in terms of binary code, the detector reads 0's and 1's. The
process is complete in approximately 10 milliseconds, a rate of 10 megabytes per
second for each page of memory.

6.5 DATA ERASING TECHNIQUE

To erase data; a brief pulse from a blue laser returns molecules in the Q state
back to the rest state. The blue light doesn't necessarily have to be a laser; you can
bulk-erase the cuvette by exposing it to an incandescent light with ultraviolet output.

6.6 REFRESHING THE MEMORY

In Protein memory the read/write operations use two additional parity bits to
guard against errors. A page of data can be read nondestructively about 5000
times.Each page is monitored by a counter and after 1024 reads, the page is refreshed
by a new write operation.



7. MERITS

Fig 5.Birge’s Memory cell

• This is based on a protein that is inexpensive to produce in quantity.

• .The system has the ability to operate over a wider range of temperatures than
the semiconductor memory.

• The data is stable, i.e. the memory system’s power is turned off, the molecules
retain their information.

• This is portable, i.e. we can remove small data cubes and ship GBs of data
around for storage or backups

• Data can be stored for years without any refreshment.



8. APPLICATIONS

Most successful applications of bacteriorhodopsin have been in the
development of holographic and volumetric three- dimensional memories.
Other applications of Bacteriorhodopsin are:-

• When nutrients get scarce, this Bacteriorhodopsin becomes a light-
converting
enzyme. It's a protein powerhouse that in times of famine flips back and forth
between purple and yellow colours. If controllable, this could be valuable
in building battery conserving and long lasting computer display panels.

• Protein’s photoelectric properties could be used to manufacture photo detectors.

• Bacteriorhodopsin could be used as light sensitive element in artificial
retinas.

• German scientists have used holographic thin films of bacteriorhodopsin to
make pattern-recognition systems with high sensitivity and diffraction-limited
performance.

• Nano biotechnology based medical diagnostics may use this proteins in imaging
devices.

• Molecules can potentially serve as computers switches because their atoms
are mobile and change position in a predictable way. By directing the atomic
motion two discrete states can be generated in a molecule, which can be used to
represent either 0 or 1. This results in reduction of size, that is, a bimolecular
computer in principle is one-twentieth of t h e size of the present day
computer.



• bR has all desired properties for usage in associative memory applications.

9. RESEARCH DEVELOPMENT

Branched- photocycle memory is developed at the W.M. Keck Centre for
Molecular Electronics at Syracuse University. This memory stores from 7 to 10
gigabytes (GB) of data in a small 1 × 1 × 3-cm3 cuvette containing the protein in a
polymer matrix Data are stored by using a sequential pair of one-photon processes,
which allows the use of inexpensive diode lasers to store one bit into the long-lived Q
state. The read/write/erase process is fairly complicated. The 10-GB data cuvettes used
in the 3-D memory described above can withstand substantial gravitational forces and
are unaffected by high-intensity electromagnetic radiation and cosmic rays. They can
even be submerged under water for months without compromising the reliability of the
data. 3-D protein memory cuvettes are already being designed and optimized for
archival data storage in office environments. Many millions of dollars have been spent
on this research and development. We have learned a great deal in recent years about
proteins and its applications.



10. CONCLUSION

Birge’s system, which he categorizes as a level-1 prototype (i.e., a proof of
concept), sits on a lab bench. He has received additional funding from the US Air force,
Syracuse University, and the W.M.Keck foundation to develop a level-2 prototype.
Such a prototype would fit and operate within a desktop personal computer. “We are a
year or two away from doing internal testing on a level-2 prototype”, says Birge.
“Within three or five years, we could have a level-3 beta-test prototype ready, which
would be a commercial product.”



REFERENCES

1. www.cem.msu.edu
2. www.ieee.org
3. www.wikipedia.com
4. Samuel Styne Protein-Based Three-Dimensional
Memory, American Scientist, pp.328-355, July-August
2002.
5. Fedrro McKenzie, A model with Protein Storage, Int. J. Quantum Chem.,
vol. 95, pp. 627–631, 2003.

6. D. A. Thompson and J. S. Best, “The future of magnetic storage technology,”
IBM J. Res. Develop., vol. 44, pp. 311–322, 2000.

7. Marques Da Silva,
“Bacteriorhodopsin as a photochromic retinal protein optical memories,” Chem. Rev.
vol.100, pp. 1755–1776, 2000.


Protein memory(seminar report)

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