FightAIDS@Home: A Layperson's Explanation
AIDS stands for "Acquired Immune Deficiency Syndrome." AIDS is caused by a virus called HIV — the Human Immunodeficiency Virus. When a human body is infected with HIV, it will work to fight the infection by making "antibodies," special molecules that are supposed to fight HIV.
Having HIV disease — or being HIV-positive — is not the same as having AIDS. Many people live with HIV, and do not get sick for many years. However, because the human body cannot generate antibodies that can eradicate HIV, as HIV disease continues, it slowly wears down the immune system, infecting key cells of the immune system and impairing their function or even destroying them. Eventually, HIV infection results in progressive depletion of the immune system, leading to "immune deficiency." The immune system is said to be "deficient" when it can no longer fulfill its role of fighting off infection and cancers. People with cellular immune deficiency are much more vulnerable to very rare infections such as tuberculosis, which can spread and mutate into drug resistant forms.
HIV remains a difficult target to stop because when it replicates, it does not do so perfectly and is thus continually changing. Scientists — like those at The Scripps Research Institute — have been studying HIV intensively to find ways to stop the onset of AIDS. The FightAIDS@Home Project is searching for drugs that can disable a key step in HIV's life cycle — specifically by blocking HIV-1 protease.
Blocking HIV Protease
Proteins are the basic building blocks in all of life's functions. (You can read more about them in the description of the Human Proteome Folding project.) Proteins are long chains of smaller molecules called amino acids. Enzymes are particular kinds of proteins that accelerate biochemical reactions. A protease ("pro-tee-ace") is an enzyme that is able to cut proteins apart at some point along the amino acid chain. For example, when you eat food containing protein, the protein molecules are cut apart into smaller amino acid molecules by proteases in your stomach. Your body can then use the amino acids to build the proteins it needs. While only a small percent of all of the proteins in an organism are proteases, they are very important in the proper functioning of its life processes.
But not all proteases are good. HIV makes and uses a particular protease, HIV-1 protease, which it uses to make the virus's different proteins.
This is where ligands play an important role. Ligands are small molecules that come from outside the cell that attach, or "bind," to pockets in proteins. These pockets are sometimes called receptors. You can think of a ligand binding to its receptor like a key fitting into a lock. The FightAIDS@Home Project is searching for ligands (drugs), which can attach to the HIV-1 protease receptor in a way that blocks its ability to function as an enzyme. This prevents the virus from spreading further in the body and developing into AIDS. Molecules that block HIV protease are called "protease inhibitors."
Your device will help by simulating the attachment process (docking) of many ligands to the HIV-1 protease, using one of two computer programs called AutoDock and Vina. The most promising ligands will be studied in more detail by scientists and should lead to better protease inhibitor drugs for controlling HIV and ultimately preventing the onset of AIDS.
For more about the agent running the FightAIDS@Home project, click here.