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Get Yourself Into Folding At Home---it's Scientific!

Updated on February 10, 2015

It's Just What Proteins Do & We Can Help the Scientific World Use Our Computers

If it were up to me, I would have named this process "Protein Spiraling," but the scientists got to it before I did!

So a relatively formless, flat-like, cooked-spaghetti looking, polypeptide string suddenly can't resist "folding" and it springs into action and the result looks like this.

What do I care about protein folding? My ears have been picking up on medical talk over the media, regarding new discoveries that might solve some puzzling and devastating medical conditions - why they happen, how they happen, and why so many of us get a condition called Peripheral Neuropathy that is wreaking havoc in my life!

Read about my discoveries here. Peripheral Neuropathy It's not a cool condition - pains are many, complicated and hot!

Now, back to Protein Folding. This is the name of the physical process that grips that polypeptide, and results in its "folding" (spiraling) into a characteristic 3-d structure that performs and functions like that particular protein. This and every protein exists in that stringy polypeptide form, what they call a random-coil after it has converted from its mRNA sequence into a 1-d amino acid chain.

It is Amino Acids that act on the polypeptide that cause it to curl up into a 3-d form with a dependable complexity. Now I would call the "stringy" part on the left the native state of this polypep, but I'd be wrong. The native state of the protein is the curlique on the right.

The result of the "folding" is a particular 3-d form, and irregularities or bends where they don't belong, termed "failure to fold into native structure produces inactive proteins" and these inactive gems are likely to be toxic proteins. (Is this what makes parts of some potato skins green?)

Seriously, we don't want inactive proteins; we want the 3-d structure indicative of functional proteins. (for the most part, nearly every element of functional proteins "folds," however some parts do not.

Specifically, the build-up of amyloid fibrills, resulting from wrongly folded proteins, leads to neurodegenerative (and other) diseases, studies are leading scientists to believe. Even allergies require misfolded proteins, to activate, because the immune system provides antibodies that only recognize properly folded proteins.

A public domain illustration of the process of protein folding - Chymotrypsin inhibitor 2.

Why & How Does Protein Folding Occur?

in the presence of water,

These proteins exist in their primary structure (this is their amino-acid sequence), also called native conformation. During the Biosynthesis process the protein molecule does its involuntary folding.

Necessary components of the convolusion are H2-0, both in the solvent (water or a lipid bilayer), the salt concentration, hot warm or cold it is, and the presence of specialized molecules which either help or hinder the folding.

Public domain illustration of a lipid bilayer (made of phospholipids in the highest congregation), that - once they are doused with a water bath - form up with their double-tailed ends pointing into the center of their gathering ground (sheet) .

These active little fellas squiggle in close to each other and help provide an impermeable barrier to offensive substances that might prevent the Protein Folding from taking place.

Let Me Ask You

Do you know what protein folding is all about?

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Protein Folding Video

Water's Role in Protein Folding

Molecular Theory of Water and Aqueous Solutions <br> Part II: The Role of Water in Protein Folding, Self-Assembly and Molecular Recognition
Molecular Theory of Water and Aqueous Solutions <br> Part II: The Role of Water in Protein Folding, Self-Assembly and Molecular Recognition

This book starts out by presenting the evidence for the importance of Hydrophilic interactions in biochemical processes and then goes on to describe the applications of the hydrophilic interactions in these processes, specifically protein folding, protein association, self assembly and molecular recognition.

In this volume it is shown that the new paradigm, based on the hydrophilic effect, brings us as close as one can hope to the solutions of the protein folding problem, as well as the problem of self assembly and molecular recognition. In addition, the new paradigm also provides an explanation of the high solubility of globular proteins.

The change in the paradigm is shown symbolically in the cover design of this book.

 

Protein Folding Occurs During or After Biosynthesis

in biosynthesis cells produce or construct proteins

Protein Biosynthesis is a step once-taken, seldom to be reversed, and that is why protein types can be studied at all. It is rather like dressing for success, all suited up, and stepping into a puddle that turns out to be a pond which swallows you, white suit and all.

You can climb out, but you can't undo the fact that you will be forever skittish about stepping into a puddle again - well, it's not quite like that.

Protein Biosynthesis is more like a human body's process of puberty - depends on the production of hormones - and once the sexual-maturity-folding happens - it has happened!

There's no becoming a kid again; however, both proteins and people can suffer from disruption in their proper functioning, people from too little or too much hormone, proteins of temperatures that rise or fall out of the optimum range for folding, and other extremes. But, for normal processes to take place and remain strong in the new folded form certain conditions are necessary for proper use of the protein in question.

Primarily, in folding the particular protein's amino-acid-sequence stipulates the confederation of: 1) native state, and 2) the proclivity to reach the native state.

Visualize These Project Images

Visualize These Project Images
Visualize These Project Images

See Likeness of Project Images Above

if you like the looks of these complicated strings - give it a try

The videos show you how to grab parts and sections of the images and attach features, which you then manipulate and run through the game's system, all to the accompaniment of rising or lowering scores. Pretty Nifty! Diagram by Yikrazuul commons.wikimedia.org

Oxidative Folding of Peptides and Proteins

Oxidative Folding of Peptides and Proteins: RSC (RSC Biomolecular Sciences)
Oxidative Folding of Peptides and Proteins: RSC (RSC Biomolecular Sciences)

This is the first monograph to provide a comprehensive overview of this exciting and rapidly developing area. It offers in-depth insights into the mechanisms of in vivo and in vitro oxidative folding of proteins as well as mono- and multiple-stranded peptides. Procedures applied for laboratory and industrial purposes are also discussed by top experts in the field.

The book describes the enzymes involved in the correct oxidative folding of cysteine-containing proteins in prokaryotes and eukaryotes. It then goes on to discuss the mimicking of these enzymes for successful in vitro folding of proteins (including synthetic replicates) and to deal with important issues concerning cysteine-rich peptides.

The ability of natural bioactive peptides to fold correctly, and in high yields, to form defined structural motifs is still puzzling. With this in mind, synthetic procedures for establishing native cysteine frameworks are discussed using selected examples, such as the potential of selenocysteines.

 

Look at How This Game Project Works on Your Home Computer

Structure & Mechanism of Protein Folding

Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Folding
Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Folding

Fersht's Structure and Mechanism in Protein Science is a defining exploration of this new era, an expert depiction of the core principles of protein structure, activity, and mechanism as understood and applied today.

A thorough recasting of Fersht's previous text, the book takes a more general look at mechanisms in protein science, emphasizing the unity of concepts in folding and catalysis and the importance of the relationships between basic chemistry, kinetics, thermodynamics, and structure.

 

Secondary & Tertiary tRNA Structure

Secondary &amp; Tertiary tRNA Structure
Secondary & Tertiary tRNA Structure

Foldit Project Explanations & Games

learn about protein folding and this opportunity to play

I heard about Foldit on NPR and since I'm not a gamer, at first I thought it didn't have any resonance to me, until I heard the part about Protein Folding.

Well, I've become slightly acquainted with Protein Folding due to my interest in revering polyneuropathy (nerve damage), in some cases caused by toxic chemotherapy drugs (they are all toxic). So I listened more attentively.

I wasn't the only one who had any amount of skepticism about this game concept, and the others held science smarts superior to me. The Scientist, Magazine of the Life Sciences, features Andrea Gawrylewski's 5/23/08 article, "Foldit for fun" about the then recent phenomenon.

The game is a result of co-founder David Baker's team of scientists at the University of Washington, coupled with computer programmers, garnering info from Rosetta@home.

The premise of Foldit is simple:

See protein floating on screen.

Drag parts of protein around to get it to the optimal energy state. The better the energy, the more points you get.

But in order to make that happen, you must rearrange amino acid chains attached to the protein backbone, making sure they aren't hitting, or "clashing," each other and sending out spinning red stars on the screen.

Read more: Foldit for fun - The Scientist - Magazine of the Life Sciences

The Scientist

From Foldit!! Competitive Protein Folding - this is real science you play like a game

Use the tools to enter into a game to solve a Protein Folding puzzle while you earn points for all your smart moves. Expert players demonstrate their skills as you watch them earn points.

Protein Folding, Misfolding, and Disease

Protein Folding, Misfolding, and Disease: Methods and Protocols (Methods in Molecular Biology)
Protein Folding, Misfolding, and Disease: Methods and Protocols (Methods in Molecular Biology)

Protein misfolding is a key feature of many disorders in humans, given that over twenty proteins are known to misfold and cause disease.

In Protein Folding, Misfolding, and Disease: Methods and Protocols, experts in the field present a collection of current methods for studying the analysis of protein folding and misfolding, featuring strategies for expressing and refolding recombinant proteins which can then be utilized in subsequent experiments.

 

Protein Folding Science & Game at Once! - do real science, solve problems, help out

If you have good visual memory, good spatial vision, this may be the game for you. Although this idea is new to me, you may have some acquaintance with the idea, but have never got into puzzling. This session was done at UW in 2009.

Molecular Chaperones and Protein-Folds Catalysts

Guidebook to Molecular Chaperones and Protein-Folding Catalysts (Sambrook & Tooze Guidebook Series)
Guidebook to Molecular Chaperones and Protein-Folding Catalysts (Sambrook & Tooze Guidebook Series)

The precise shape of a protein is a crucial factor in its function. How do proteins become folded into the right conformation? Molecular chaperones and protein folding catalysts bind to developing polypeptides in the cytoplasm and ensure correct folding and transport.

This Guidebook catalogues the latest information on nearly 200 of these molecules, including the important class of heat shock proteins; each entry is written by leading researchers in the field.

 

Do You Already Know Fold-it, the Game?

Have You Played the Foldit!! Game Yet?

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Proteins - Background for Understanding

getting started with the foldit games project

Proteins are the operative factors in every living cell, numbering over 1 to the 12th, 13th, on up.

Proteins utilize the carbs we ingest prior to exercising, but not before they break them down and send the food through our digestive systems, in the smallest increments. No matter what the kind, all proteins consist of long amino acid strings.

Each protein chain folds up on itself in a unique set of bends. Occasionally a protein mis-folds, leading to release of toxins, allowing illness or other conditions that lead to ill health or even death.

Healthy chains consist of molecules joins one to another, and periodically dangling a small string of atoms. The main string is called the "backbone" and the side string is called a "sidechain."

Characteristic of each variety of protein is the "fold" into which they bend themselves, the same shape every time (with few malfunctions), due to their proclivity to resist remaining in a straight line.

I always thought a protein was a protein, and an enzyme was an enzyme, but it turns out that proteins can do the work of enzymes, acting as catalysts to help chemicals zip through their reactions, doing their jobs.

Proteins serve our bodies in so many functions:

Begins to convert food starch into usable forms

Converts alcoholic beverages into the form the human body can metabolize for energy

Transports oxygen through our bloodstreams

Scabs over a wound providing protection for healing

Collagen provides foundation for everything from skin to bones

Serves as muscle protein

It's also the growth hormone that creates adults out of kids

In potassium channels, signals circulate through the nervous systems

As insulin, they govern blood sugar levels, both positive and negative aspects

The Foldit game provides players an opportunity to predict the structure of various proteins. Knowing the structure that is just right is a critical challenge in fighting and correcting the problems associate with diseases and conditions that afflict millions.

Gamers can even try their hands at designing "new" proteins that could be helpful in disease prevention or remediation. How? By clicking and dragging, and submitting their trials into the program so it can do its trick. The three main areas of concentration are HIV/AIDS, Cancer and Alzheimer's Disease.

Learn a certain amount of science as you build your gaming skills, and get rapid feedback.

What Do You Think?

Are you ready to get going with gaming now?

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Links to Foldit!! Supercomputer Folding Project

that's an asymmetrical retroviral structure you're looking at

I downloaded Foldit., 46.5MB for the Mac, in a few minutes. Now if I can stop.

I downloaded BOINC at boinc.berkeley.edu

BAM, or BOINC Account Manager, makes it easier to manage a player's preferences, teams and project choices. I considered creating a BAM account here boincstats.com

I went through a number of steps, agreed to the rules of the road, and can begin working on a project at my leisure.

Diagram at en.wikipedia.org/wikia>

Macs Serve You Right for Folding Gaming - I can't imagine not having a Mac

Apple iMac MC813LL/A 27-Inch Desktop (OLD VERSION)
Apple iMac MC813LL/A 27-Inch Desktop (OLD VERSION)

New iMac features next-generation Intel Core i5 quad-core processors and the fastest graphics ever in an all-in-one computer. It also brings Thunderbolt I/O technology to the desktop for lightning-fast data transfer, a new FaceTime HD camera lets you make full-screen HD video calls. All from a beautiful, widescreen 27-inch LED-backlit display that takes up just a sliver of your desk. It's everything you want in a desktop.

 

Misfolding & neurodegenerative diseases - Kindle Edition

Protein folding and misfolding: neurodegenerative diseases: 7 (Focus on Structural Biology)
Protein folding and misfolding: neurodegenerative diseases: 7 (Focus on Structural Biology)

The worldwide increasing age of populations brought the neurodegenerative diseases into the focus of interest. A number of the diverse human neurodegenerative diseases are now recognized as conformational diseases frequently caused by aggregations of unfolded or misfolded proteins.

Knowledge on the intrinsically unstructured proteins, a new family of gene products as well as on the misfolded proteins produced by genetic mutation or environmental effects has been extensively accumulated in the past years.

 

Project Gaming Brings Scientific Advance

gaming that really counts

What do gaming and degenerative nerve diseases have in common with chiropractic? Protein-Folding Gamers work on online games, seeking solutions to scientific puzzles - to which the answer is not yet known.

Through gaming some of the same type of discoveries on mis-folding that causes neuropathies - as have been made on AIDS puzzles.

Many individuals with diabetes, HIV, and those exposed to chemo-like toxins are some of those who can benefit from results of these games.

This link takes you to my 4th Peripheral Neuropathy lens, that explains some modalities chiropractors use to treat PN in patients. Treat PN With Chiro

What Do You Think of This Idea of Online Gaming for Science?

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    • Ram Ramakrishnan profile image

      Ram Ramakrishnan 5 years ago

      It is a great idea for those interested in science.

    • TransplantedSoul profile image

      TransplantedSoul 4 years ago

      Ha Ha - at first I thought this lens was going to give some Laundry Folding tips (I am hopeless), and then for home-pasta making... quite a surprise.

    • profile image

      athrunzala 4 years ago

      nice lens, learned a lot on tips!

    • RosaMorelli profile image

      RosaMorelli 4 years ago

      Wow, this is such a detailed and informed article. I've mentioned on your peripheral neuropathy Lens that I have something similar, so I'm fascinated by this one. I can't take it in all at once (I'm a bear of little brain!) but I'll definitely be revisiting this (got it bookmarked and everything :) to re-read and understand it more closely. Many thanks for doing so much research on this and providing so much in-depth information.

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