I’m going to start with an analogy. Imagine you are the leader of an anti-terrorist strike force. (Maybe some of you actually are!) Your team starts to receive warnings that a terrorist group has moved into the area. You start to see signs of their presence. You capture a few of their underlings, and give comfort to those innocents that the terrorists have attacked, but you never really make a dent in the enemy organization. Finally, you get lucky, and receive word that their big leader is in the area: the guy who really runs things. You don’t strike right away – you lay low, gather intelligence, and then hit the leader in precisely the right way to bring about his downfall and demise. The whole terrorist network unravels after that.
This seems like a perfectly reasonable situation and approach to a problem. It mirrors the situation that scientists were recently facing concerning the molecule named “FAAH” (fatty acid amide hydrolase). FAAH is an enzyme naturally found in our body. Enzymes are Natures way of making chemical reactions go faster. Without something exerting a fine degree of control, chemical reactions may not produce exactly what you intended – which could be fatal, if a crucial part of your cells is not produced 100% accurately. Enzymes ensure that everything goes exactly according to plan.
Unfortunately, pain is a natural, and desired, bodily sensation. Desired by our bodies, in any case. Pain is the bodies way of signalling injury and it is what warns you that you’ve just put your hand on a hot object – you can then snatch your hand away before suffering serious harm. Without this pain sensation, we would likely die of infected wounds and broken bones that we didn’t even know we had. However, for patients which have already sought and obtained medical attention and for patients with long-term (chronic) pain which has already received attention from a doctor, pain is entirely undesirable. It’s important to know you’re burning your hand but it’s not really important for you to still feel that gunshot wound twenty minutes after you’ve been moved onto a hospital bed and are receiving treatment by a large team of doctors.
That’s where pain medications come in, of course. However, currently most of our best pain medications either come directly from Nature or are based on the pain medications from Nature (the opioids). They do a good job on pain, but are seriously addictive and come with negative side-effects such as respiratory depression and unconciousness. We need something better. That is where FAAH comes in. FAAH is one of the molecules that Nature uses to signal pain. Its activation begins the nerve sequence that results in us suffering from pain. Normal pain medications simply dull and supress the pathway that this signal takes along the spinal cord, on its way to the brain. This is equivalent to my analogy above, where we simply arrest and detain the followers of the terrorist leader, making it more difficult for him to get things done. We still aren’t doing anything about him – about FAAH. We needed intelligence gathering to tell us precisely how to strike at him.
Well, that intelligence has now been gathered. Scientists report in the journal Chemical Communications that they have used advanced computer simulations to decipher the molecular shape of the FAAH enzyme. More importantly, they have deciphered the exact shape of the “bullet” needed to kill it: only the correct carbamate enzyme inhibitor with the precise shape and orientation is able to bind to the FAAH enzyme and shut it down, which halts the pain sensation. Now that scientists know the “shape” of the inhibitor needed, they can give that information to synthetic organic chemists who will synthesize the necessary molecule in the laboratory. This molecule can then be used as the foundation for an entirely new generation of pain inhibitors that don’t have the side effects of the opioids.
This molecular modeling work is just one example of how powerful computer simulations can not only advance our understanding of science, but also improve our quality of life. As someone who suffers from chronic pain, I find this to be a wonderful achievement.
The source of this article can be found at: http://www.rsc.org/Publishing/Journals/CC/article.asp?doi=b714136j