Hi Rbolo and Dr Perryman,

Rbolo, I remembered reading something on Wired's science pages a while ago and found it for you. I don't know if it is anything like what you were meaning before but the link is here

http://www.wired.com/science/discoveries/news/2007/11/laser_virus

Cheers for the excellent explanations Dr Perryman.

Slap

Hello, Slapshot

Thanks, I had read the article on the pulsating laser before. What I'm talking about, did involve some special type of sound frequency and something to do with a resonant frequency. The name and description of the article, was a bit more technically, however.

It didn't say if they used a pulsating modulation or even what frequency they used. I'm a bit skeptical on how sound could achieve the very high 'selective' frequency needed for resonsance of such a small particle. I'm sure someone really good in mathematics could calculate the resonant frequency? Also, one of the articles I found and posted involved using electromagnetic radiation as a resonant source.

Even if sound could destroy virus particles, I have doubts on how that could be applied to the entire body effectively. If there is just one virus particle left then your quickly left back at square one anyway.

Obviously, the best approach to a problem like HIV is 'combination therapy' usually in the form of multiple drugs working at different levels to interfere with the virus 'life cycle.'

I believe Dr. Perryman stated, the problem with drugs used for RNAi is they cannot effectively penetrate the cell walls at this time. I think RNA interference holds a lot of promise if they can ever achieve that effectively.

I wonder if it is possible to use of the same chemical docking strategies to enter cells like viruses(nature) use in order to delivers drugs?

Or hollow out a virus to deliver the drugs?

I have some doubts, but was just a thought!

Hi Robert,

You're very welcome.

Thank you for helping me perform these calculations,
Dr. Alex Perryman

Hi rbolo,

To perform these docking calculations well, we first need to have a very high-resolution 3-D structure of the target (that is, a three-dimensional map with a tenth of a nanometer scale of the location of each and every one of the many thousands of atoms that form even a small protein). And then we need to understand the amount of flexibility in the target, in terms of which regions are moving, how far they move, and how fast they move (in relation to each and every other atom in the target).


Atomically-detailed maps of the structures of a human cell do not yet exist. Thus far, scientists have only solved the structures of a fraction of the different pieces. More and more structures of how a few of the different pieces fit together to form a larger complex are being solved each year. These larger complexes can form the building blocks for even larger structural components of the cell or the environment outside of it, and sometimes they form very intricate little nanomachines (such as the ribosome, which is the molecular factory that synthesizes proteins by using the information contained in "messenger RNA" as a guide...........many, many labs worked for decades to try to solve the 3-D structure of the ribosome, and it was only recently figured out). The science still has a long way to go, and a lot of time and effort needs to be spent before we'll have a better picture of the structure of a human cell. Without those details, these types of docking calculations cannot be applied.

Thus, these calculations help us understand how a compound is able to bind to and sabotage its target, and they can help guide the process of designing and evaluating new compounds. But these calculations involve the events that happen after a compound has already been digested, entered the bloodstream, diffused to the cells that contain the target, entered the cells, and then approached the target (which is usually in a very densely-crowded environment with many other somewhat similar targets that you don't want to hit). These other events are currently far beyond the scope of atomic-level docking calculations (as far as I know). Dealing with these issues tends to involve a lot of expensive, time-consuming trial-and-error experiments with cells in test tubes, then in different animals, and then in people who volunteer. But the physicists, mathematicians, chemists, biologists, biochemists, and computer scientists who are becoming increasingly interested and involved in studying these questions keep surprising me. Who knows what will be possible with the simulations that will be performed a few decades from now?

As a note, a large part of Prof. Art Olson's Molecular Graphics Laboratory at TSRI is devoted to working on creating, developing, validating, applying, and sharing the different tools, techniques, and theories that deal with these specific docking questions. This type of work forms the foundation for and will help inspire the types of advancements that might one day make simulations of those other, more complicated events possible.