Cloud computing-Role in Drug discovery

Cloud computing can be the drug discovery game changer as foreseen by Paul Davey -the chief executive officer at InhibOx Ltd.Nimbus Thinks It Can Cure Obesity With Cloud Computing; Next Up, an Exercise Pill....
iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan.The Virtual Laboratory Project is working to enable "Molecular Modelling for Drug Design" on the World Wide Grid...
iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. It is believed that this web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/ .

Let’s start with a refresher, and make the link between high-throughput screening, computer-aided
drug discovery and cloud computing along the way. The scientists behind developing CADD systems have always been grasping for more computing power, to make practical their developments. Ten years ago, Professor Graham Richards at Oxford University was leading the screen-saver project (9), pulling spare CPU power from over three million PCs across the world to drive virtual screening of cancer drug candidates. Cloud computing makes that amazing vision a practical, commercial reality. At last, computing power is available and cost-effective enough to cause the design of
modelling systems to be fundamentally reassessed. It should herald the development of no-compromise
CADD and effective virtual screening – and that could indeed change the drug discovery game.

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Cloud-Driven Biopharmaceutical Company

Ariel Schwartz at FastCompany recently profiled Nimbus, a biopharmaceutical company that is making big waves in the drug discovery space. The firm has made announcements about pending developments in obesity and lymphoma-fighting drugs. While there are already numerous efforts underway to tackle these conditions at any number of other pharmaceutical companies, Nimbus has a particularly “nimble” drug discovery model that hinges on cloud computing.Nimbus has garnered some significant attention as of late beyond its upcoming obesity pill that aims to mimic the effects of exercise by preventing new fat and burning that which is stored. The company just received an undisclosed amount of financial backing from Bill Gates. Another contributor to the seed round was Dr. Richard Friesner, who founded the computational drug design company Schrodinger. 

According to the Schwartz, “The company’s secret sauce is its computer-inspired drug discovery approach, which uses cloud computing to simulate what a drug target looks like. This allows the company to do research overnight that would take months at other pharmaceutical companies.

During the brief interview Nimbus suggested that another ingredient of their secret sauce is that computational scalability and flexibility using the cloud model allows for more agility to consider a more extensive set of options during modeling and drug discovery.  In this case, the Nimbus process is unique in that it is able to consider the important role water plays during absorption of a drug since it can determine how well the drug is retained. 

According to Nimbus, this is something many companies cannot (or do not consider) because of the massive computational requirements it takes to factor this into the equation.

As the company’s Chief Business Officer, Jonathan Montagu noted, “It’s the difference between Google Maps and Google Earth…most drug companies have a two-dimensional view, but we have an understanding of how water molecules in a protein target impact drug binding. This gives you more of a three-dimensional representation of how a drug target works.”

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Cloud computing

Step-by-Step: From Virtualization to Cloud.

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Genome Sequence Could Reveal 'Achilles' Heels' of Important Wheat Disease

Research published in PLoS Genetics on June 9 provides insights into how an important fungal disease is able to evade wheat's defences. The researchers hope that the study, which reveals the fungus' complete genome sequence, will enable them to breed resistant crop plants or improve the use of pesticides.

The genome sequence was produced by an international consortium of researchers including scientists at Rothamsted Research in the UK. The scientists, who were funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and others, are already using the fungus' genome sequence to find ways to control the disease in order to help meet the challenges of ensuring global food security.

The consortium has sequenced the genome of a fungus called Mycosphaerella graminicola which causes leaf blotch disease in wheat. The disease kills cells in the plants leaves leaving large dead blotches which are unable to absorb energy from the sun. This significantly reduces yields and takes a serious toll on wheat crops globally and in the UK; annually a 5-15% reduction in grain yield is incurred in each wheat field solely as a result these infections.

Professor Kim Hammond-Kosack of Rothamsted Research who led the study in the UK said "M. graminicola attacks wheat plants by stealth. There is normally a period of about a week between when a plant first becomes infected and when the characteristic blotches of the disease appear on its leaves. During this time it appears that the plant fails to recognise it has become infected and so is unable to activate its defences to fight back. Studying the fungus' genome will help us to understand how the pathogen is able to go undetected and maybe reveal a chink in its armour that we can exploit."

The genome sequence reveals that M. graminicola has very few genes which produce enzymes able to break-down plant cell walls compared with other fungi which specialise in infecting plants. Plants often use the presence of the sugars and proteins released when a cell is broken down as cue for turning on their immune responses, so the researchers think that the unusually low numbers of genes producing enzymes for breaking down plant cells may be crucial to the fungus' stealth approach.

The team from Rothamsted have already started on work using the genome to look for potential weaknesses in the fungus' defences. Collaborating with researchers at Wageningen University in the Netherlands they have identified a protein in the fungus which is important in keeping it hidden. This research was published recently in Plant Physiology.

Dr Jason Rudd who worked on the project at Rothamsted Research said "We were able to use the information in the genome sequence almost immediately to look for a potential Achilles' heel. We singled out a protein which helps keep the fungus camouflaged and protects it from the plant's defences. When we generated a mutant strain of the fungus which didn't contain the gene for this protein, the infected wheat plants produced strong immune responses and didn't develop the characteristic leaf blotches. Our next step is to use these and similar findings to help farmers combat this disease out in the field in order to reduce wheat losses."

Professor Maurice Moloney, Director and Chief Executive of Rothamsted Research commented "Rothamsted Research is proud to be part of the team that has sequenced and analysed the M. graminicola genome. This fungal pathogen causes one of the most pernicious plant diseases and accounts for significant losses annually in wheat yields throughout the world. This work illustrates the power of sequencing the genomes of plant pathogens in identifying key targets for efficient plant protection."

Professor Douglas Kell, Chief Executive of the Biotechnology and Biological Sciences Research Council, said "Genome sequencing is an important tool in the fight to ensure global food security. Determining the sequence of a destructive crop disease like this is now so quick and affordable that it can be viewed as a research tool rather than a project in itself. This is especially true when the complementary talents of researchers in different countries can be brought to bear. As in this project, this information can be put to immediate use in finding new ways to combat plant disease."

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Software review:VNL and ATK(nanotechnology)

QuantumWise provides two different interfaces for performing electronic transport calculations:

·         Virtual NanoLab (VNL)

·         Atomistix ToolKit (ATK)

Virtual NanoLab (VNL) is a graphical user interface (GUI), and Atomistix ToolKit (ATK) is the script-based interface. Which of the interfaces to use, is sometimes a matter of taste, and sometimes determined by the task at hand. VNL is the most appealing option, because of its intuitive ease of use. Some prefer ATK because it gives more control and flexibility through scripting.

A modeling study generally consists of three parts:

·         Setting up the calculation

·         Running the calculation

·         Analyzing the output of the calculation.

User can get control of these steps using ATK, often in combination with VNL.

Virtual Nano Lab:

VNL allows to:

·         design nanosystems

·         Set-up and execute numerical calculations

·         Visualize the results

·         Graphical user interface-easy to use

·         User friendly approach to atomic scale modeling

·         Contains a set of interactive instruments

Its main advantage is to provide 3 D visualization tool Nanoscope to view and analyze the atomic geometries and computed results.

Applications:

• Calculation of transport properties of two-probe systems under an applied bias voltage
• Calculation of energy spectra, wave functions, electron densities, atomic forces, effective potentials etc.
• Calculation of spin polarized physical properties
• Geometry optimization

Calculations:

It calculates:

• Electronic Structure
• I–V Curves
• Schottky Barriers
• Conductance
• Contact Resistance
• Tunnel Magneto-Resistance
• Effect of doping/defects
• Charge Stability Diagrams

Samples:

The sample can:

·         model isolated molecules as well as periodic systems such as

            – Molecules

            – Nanotubes

            – Crystalline systems

·         Can model complex nanostructures that combine molecules with periodic

systems and macroscopic elements

           – Two probe systems (electrode-nanostructure electrode systems).

Unlike ATK: it calculates several physical quantities without the need to specify them

explicitly:

      • ElectronDifferenceDensity

      • ElectrostaticDifferencePotential

      • Total Energy

Atomistix Tool Kit:

It is a:

·         Numerical engine that carries out the actual simulations

·         Ab initio electronic-structure and transport calculations

·         Python based Nanolanguage scripting environment-more control and flexibility

·         First principles electronic structure program

Unlike VNL: it gives more control and flexibility through scripting.

Key Features:

·         Calculation of electronic properties

·         Access to DFT algorithms

Quantum Mechanical models in ATK:

·         Density Functional Theory (DFT)

·         Non-equilibrium Green’s Function/Equilibrium

·         Green’s Function

·         Pseudopotentials

·         Numerical basis sets

·         Semi-empirical models

References:

·         http://www.quantumwise.com/products/download

·     http://www.quantumwise.com/documents/manuals/latest/VNLTutorial/index.html/chap.intro.html#sect1.intro.atk

·         http://ece.vnit.ac.in/vlsi/VLSI_LAB/simulation_tools_for_nanoelectronics.pdf

·         http://www.quantumwise.com/documents/manuals/ATK-2008.10/chap.intro.html

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Water,governance and corruption-Pakistan

This is a review of the essay by Feisal khan; from the book “Running on empty-Pakistan’s water crisis” published by Woodrow Wilson International centre for scholars. Feisal khan is assistant professor in the Department of Economics at Hobart and William Smith Colleges.
In the article ,Feisal khan highlights the major factors behind the brutality of the Pakistani water crisis and attributes these factors to a historical legacy of bad policies, misgovernance, and corruption.
He starts with the narration of 2005 analysis of the Pakistani water situation by the World Bank. The facts and figures mentioned are very distressing. Pakistan seems to be one of the most arid and water-stressed countries, on par with those of the Sahara Desert. A per capita annual water availability of 1,000 cubic meters (m3) is believed to be low enough to “impede development and harm human health”. Indeed, in one important sense, the story of Pakistani agriculture is a story of declining farm-gate. The author has represented the declining per capita water availability in Pakistan graphically. The graph shows water availability of 3000 m3/capita/year to less than a 1000 in 2035.The comparison of yields and water productivity of wheat in USA, Pakistan, and India shows the clear difference in outputs of wheat crop per hectare. Seven tons/ha is obtained in USA,3.9 tons in India and just 2 tons in Pakistan.
Pakistan’s wheat yield is low as compared to US and the yield of Punjab which represents the breadbasket of Pakistan is approximately half than that of Indian Punjab.
Considering the importance of water to Pakistan’s economy and its relative scarcity, water conservation and use-efficiency should be high on Pakistan’s list of national priorities but they are not. A major factor behind the severity of the Pakistani water crisis is a historical legacy of bad policies, misgovernance, and corruption.
Work on the Pakistani irrigation system was started by the British colonial administration and Pakistan had an extensive and well-developed irrigation structure with provincial irrigation departments of considerable technical expertise and professional ability after the independence. Soon after independence, India started tempering with the Pakistan’s water resources. In 1948, India shut down water flow to Pakistan in 1948. The Punjab Irrigation Department rapidly dug the 100-mile Bombanwala-Ravi-Bedian-Dipalpur canal to divert water from the Ravi to the Sutlej River, thereby forestalling another Indian attempt to cripple Pakistan by shutting the downstream flow of the Sutlej.


Basically the colonial-era irrigation department focused on technical administration and water project construction, with virtually all decisions made internally and without any user input into the decision-making process. The colonial-era Canal and Drainage Act of 1873 gave the state all rights and authority over water issues. The legal lack of rights for the water users was more strengthened by government of Pakistan amendments that stripped the Act of the extremely limited redress available to water users—i.e., farmers. This was done to consolidate power of loyalist large land owners and micromanage small farmers. This situation has remained till date and irrigation official power has remained unchecked.
In 1959, Military govt. of General Ayub established WAPDA to plan and implement a strategy for Pakistan’s water resources. As part of the water-use planning policy, the riparian dispute with India were resolved with the signing Indus water treaty in 1960.After Indus water treaty, Mangla and Tarbela dams were established. These were highly successful projects with extensive economic benefits for the Pakistani economy.
The bad policies responsible for water crisis include inadequate infrastructure investment, especially in maintenance and repair. World Bank characterizes Pakistani government policy as “Build/Neglect/Rebuild,” where all basic maintenance is literally ignored until the infrastructure is on the verge of collapse. The Promotion of sugar cane cultivation has a negative impact on the already precarious water situation as well. Besides that ;massive diversion of river waters into agriculture has led to a decline in the lower Sindh wetlands, the Indus Delta mangrove forests, and coastal fishing, as well as taken a horrible toll on the biodiversity and fauna of the entire Indus Basin ecosystem. All this has exacerbated a bad water situation, and decades of neglect have allowed major problems to reach near-catastrophic levels.
The water bureaucracy is notoriously corrupt. There is no effective internal administrative check on decisions made by irrigation bureaucrats. Second, they are more vulnerable to pressure to “accommodate” large local landowners and politicians. The level of money involved is staggering. The senior officials pay “crores of rupees” to obtain desirable posts and turn down “clean jobs at four times the [official] salary” because the bribe income is 5-8 times more than the clean salary. In 2002, many farmers were charged an annual “fee” of Rs. 30,000 for each watercourse outlet.With about 60,000 outlets in the irrigation system, this gives an income of roughly Rs. 1.8 billion to be shared among irrigation officials. And this is just for having a water outlet that gets some water at some point. This fee did not entitle a farmer to more than one’s share.At least 25 percent of farmers report bribing irrigation officials for irrigation water, with the typical payment averaging about 2.5 percent of income/hectare.
Nawaz sharif made an effort to reform through decentralization by implementing the Provincial Irrigation Authority Act of 1997.But in practice ,nothing changed because the water rights and entitlements were not on the immediate agenda of the government. The government’s habit of creating more institutions to cover the inefficiency of parent institutions is one cause of the ineffective water reforms too.


The government needs a radical restructuring of water use patterns and effective implementation to save Pakistan from disaster. We also need to eliminate corruption from the water administrating authorities. Some major reform efforts will have to be undertaken to shore up the system. The professional competence and integrity of the provincial irrigation bureaucracies need to be improved, and this will require greater centralization and reassertion of administrative control and not devolution and decentralization so that large landowners cannot threaten or bribe officials. At the same time, the government of Pakistan should also discourage sugarcane cultivation and increase the freshwater flow to the Indus Delta. The prospects for any meaningful reforms in Pakistani agricultural and irrigation administration are extremely unlikely in the immediate future. Pakistan’s water crisis and attendant misgovernance will surely worsen.

Reference:
Khan, Feisal. “Water, Governance and Corruption in Pakistan.” In Kugelman (Ed.) “Running on Empty: Pakistan’s Water Crisis.” 2009, Woodrow Wilson International Center for Scholars.

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Medical tourism in Pakistan

Medical tourism is the practice of travelling across international borders to obtain health care. It also refers negatively to the practice of healthcare providers travelling internationally to deliver healthcare. The concept of medical tourism is not a new one. The first recorded instance of medical tourism dates back thousands of years to when Greek pilgrims traveled to Epidauria for medical tourism. Pakistan is a charming and affordable destination for medical tourism and has full potential to grow further.Medical tourism in Pakistan is already arranging successful medical treatments health, care and wellness trips. Pakistan has lots of modern hospitals in federal capital city Islamabad, and two provincial capitals Lahore and Karachi. Hospitals are fully equipped with the modern means of cure, and have enough facilities and comforts for the patients. Complicated plastic and reconstructive surgeries are available in Pakistan like liposuctions, face lift and many others. Surgeons of Pakistan are dealing with the orthopedic surgeries masterly; procedures of joint replacement surgeries like knee and hip replacement surgery are available in Pakistan. Hair replacement is another strong side of medical tourism in Pakistan.www.medtravelpak.com is the forum where you can get the quality information regarding every medical procedure in Pakistan. Federal ministry of health is striving hard to meet the strict standards of health and care in the hospitals sector. There are lots of  benefits for medical tourists like in Pakistan it is easy to meet the legal requirements, visa policy is not very strict and it is easy to get the health insurance in Pakistan. No doubt Pakistan is a charming and affordable destination for medical tourism and has full potential to grow further.

Pakistan manages to make a meager amount of money despite a low cost of operations as compared to neighboring country India as it receives more than 100,000 foreign patients a year. The Confederation of Indian Industry expects the sector to grow to $2 billion by 2012. Despite that operation rates are lower in Pakistan than India and fifteenth of rates in west; the medical tourism industry is declining due to several reasons:

• organ transplant tourism: poverty in Pakistan resulted in commercializing of organs from live donors resulting in criticism from WHO and human rights organizations and transmission of HIV,hepatitis B and C viruses.
• Terrorism acts and instability in the region
• Language barrier(English is not spoken officialy in hospitals etc)
• superbug NDM-1(leading to resistance to antibiotics)
• Unaware consumers about the plethora options ( different range of packages, tourism options)
• lack of proper advertisement

Conclusion:

The Government of Pakistan and Financial institutions should invest in medical tourism.
and take steps for the up gradation of basic amenities and hospitals infrastructure.
The co-ordination between the health care and tourism sectors should be increased. Media and marketing agencies should play a positive and effective role in the marketing of medical tourism in Pakistan. We should also create a resource pool of highly skilled and cordial manpower along with standardization of services and accreditation of hospitals. Facilities with the latest equipment such as heart mapping equipment, CT Scanners, Open MRI machines, heart catheterization labs, digital ultrasound and mammogram machines and more should be introduced in the hospitals.
Organ transplant tourism should be banned and the Transplantation of Human Organs and Tissues Authority (Thota) should work properly with the total elimination of corruption and improve image of Pakistani medical tourism over the world.

References:

Facts and  figures from the Wikipedia encyclopedia

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