On our 2016 two year anniversary, we’d like to highlight some of the actual scientific progress made by the folding@home community (including the CureCoin team) since our 2014 inception:
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- Introduction
- …So how does “Protein Folding” help?
- Historical perspective using a series of Alzheimer’s Disease Studies
- FDA Clinical Trial Phases Diagram
- Folding@Home Papers since 2014
- Latest on SigmaX and CureCoin 2.0
- 2016 Business Recap
- 2016 Donation Recap
- Costs of Folding (calculator)
- IRC channel is back!
Although we’d like to take more credit, it’s humbling to be part of a global movement of teams and individuals so committed to Protein Folding research. A lot of work remains on our part to catapult the CureCoin Team to the #1 ranking – although we have managed to reach the #4 spot in under two years – beating out several large corporate-sponsored teams along the way. We envision a combination of corporate and cryptocurrency mining community interest in CureCoin are the keys to accelerating research going forward.
“We’re pushing to design drugs that are (disease) selective at higher doses, without side effects that almost kill patients” – Vijay Pande (Paraphr. CoinDesk 2013 article)
“…techniques that we develop here very naturally have been applied to cloud computing, further broadening the impact of FAH’s scientific impact.” Folding@Home blog 2016 projections
…So how does “Protein Folding” help?
Drug design has traditionally been slow, costing 100’s of millions of dollars, and is prone to stalling in Phase II trials. In projects like Folding@home, the rewards are long-term. In-silico research is done at the earliest stages of the FDA drug approval process (see figure below). In addition to the study of multiple diseases (both infectious, and proteopathy in which proteins become structurally abnormal), Folding@home’s focus is on researching protein folding dynamics. Since proteins spend up to 96% of folding time “waiting” in various “intermediate conformational states”, there are countless, as yet undiscovered molecular interactions – especially those related to drug design.
… So the answer to the original question is – “it’s complicated” – but read on for a great example:
Historical perspective using a series of Alzheimer’s Disease Studies
- In 2008, Folding@Home published a paper based on results from a study of Alzheimer’s Disease mechanisms “Simulating oligomerization at experimental concentrations and long timescales: A Markov state model approach”
- By 2012, this led to the development of a “Lead Compound” for a new Alzheimer’s Disease therapeutic strategy: “FAH simulations lead to a new therapeutic strategy for Alzheimer’s Disease – a source of a “Lead Compound”
- The drug was promising in animal models, however it failed in Phase II human trials due to a development of toxicity
- Despite this setback, the same FAH research continues to be cited by 23 studies – not all related to Alzheimer’s.
- Starting in 2015 those results are part of an ongoing research project to re-purpose an existing compound (video from ICME Xpo Talk) for use as an Alzheimer’s treatment!
Protein folding creates more opportunities in the early phases of drug design as well as enzyme research. As more computational power is added by contributors, the more “super complex systems” (like ion channels) can be explored in ways not possible a decade ago.
Acknowledgement of the Folding@Home community in Pande Lab Scientific Papers since 2014
- You can find the latest Folding@home citations on Google Scholar
- Doctor Pande’s cited works located here.
- Doctor Bowman’s cited works located here.
… be sure to also check out other scholarly works by other Folding@home associates who have co-authored these works
Conformational heterogeneity of the calmodulin binding interface
Free energy landscape of activation in a signalling protein at atomic resolution
Activation pathway of Src kinase reveals intermediate states as targets for drug design.
A network of molecular switches controls the activation of the two-component response regulator NtrC
Cloud computing approaches for prediction of ligand binding poses and pathways(credit Google)
Publicly available Papers Folding@Home since 2014 (reverse order)
Folding@home’s articles website has been moved, you can find the latest published papers here.
129. MDTraj: A Modern Open Library for the Analysis of Molecular Dynamics Trajectories.
128. Heat dissipation guides activation in signaling proteins.
127. Efficient maximum likelihood parameterization of continuous-time Markov processes
126. United polarizable multipole water model for molecular mechanics simulation.
125. OpenMM: A Hardware Independent Framework for Molecular Simulations.
124. A network of molecular switches controls the activation of the two-component response regulator NtrC.
123. Elucidating Ligand-Modulated Conformational Landscape of GPCRs Using Cloud-Computing Approaches.
122. Variational cross-validation of slow dynamical modes in molecular kinetics.
121. Revised Parameters for the AMOEBA Polarizable Atomic Multipole Water Model.
120. Markov state models provide insights into dynamic modulation of protein function.
119. Cloud computing approaches for prediction of ligand binding poses and pathways.
118. Activation pathway of Src kinase reveals intermediate states as targets for drug design.
117. Statistical model selection for Markov models of biomolecular dynamics.
116. Dynamical Phase Transitions Reveal Amyloid-like States on Protein Folding Landscapes.
115. Describing protein folding via temperature-jump two-dimensional infrared spectroscopy and Markov state models.
CureCoin Cryptocurrency Update (SigmaX and CC 2.0):
Earlier this year, CureCoin announced a change in direction for CureCoin 2.0. Rather than having a single coin, the new blockchain will result in two coins. One will be CureCoin 2.0 (purely based on folding), the other will be a traditional PoW model called SigmaX. While both will share the same decentralized blockchain model, and both will be quantum resistant and utilize Merkle Tree Signatures; SigmaX is being developed for those who feel CureCoin’s dependency on signing certificates from DCN research lacks the purity required to compete in a decentralized cryptocurrency market on its own. CureCoin holders will be allowed to participated in SigmaX based on their holdings. You can read all the details and join the sometimes colorful conversation on our bitcointalk thread
CureCoin is now available to trade on LiveCoin.net (and trading with our long time partners at Bittrex.net and Poloniex exchanges). Additionally CureCoin is listed on the CoinPayments.net marketplace which gives CureCoin the *potential* to reach a trusted network of over 31,000 registered vendors around the world. As part of the latest Fintech infrastructure, CoinPayments gives buyers and sellers peace-of mind through protected, secured transactions. Register your business to accept CURE today at CoinPayments.net!
A special acknowledgement to our top folder – Ed Olkkola, whose massive donations of CURE (generated purely from his folding activities) are helping, or have helped fund donations to ANTRUK, Bonfils.org, Pande Labs, U-foundation Zambia, and the Rwanda Dream Medical Center. We’ve chosen to start converting Ed’s donations on the markets dynamically, so you wont see a large lump-sum of coins in the donation wallets which could impact the market price if they’re sold off too fast.
What are the actual costs behind producing this much computational research through Folding@Home?
(Converting Points per Day PPD to CURE):
Estimate your own costs with our online calculator(beta)
… or see our
Dec 2015 estimates based on 12 Equipment profiles.
Please feel free to join us on the CureCoin IRC Channel for anything that’s on your mind:
A new secure bot is back online, and tipping is available.
Also, we’ve found some members use bitcointalk and other social media sites for technical support issues. If at all possible, please use our support forum instead. This helps us track tech support issues in one place, and makes them searchable for everyone with similar questions.
Thanks and Happy Folding,
The CureCoin Team