The BUNS Objective
Buried unsatisfied polar atoms (also "Buried Unsats" or BUNS) are oxygen and nitrogen atoms that don’t make hydrogen bonds. These atoms can prevent a protein design from folding correctly, so we’re introducing a new Objective to reward protein designs with no BUNS! The Buried Unsats Objective is currently available to devprev users for testing, but soon it will be released to all players!
Polar atoms and satisfaction
Most proteins are made up of just a few different elements: carbon, oxygen, nitrogen, a bit of sulfur, and lots of hydrogen. In Foldit we separate these elements into two groups: polar and nonpolar.
Carbon and sulfur atoms are nonpolar. This means they are very good about sharing electrons with neighboring atoms, so electrical charge is balanced.
Oxygen and nitrogen (and hydrogens attached to these) are polar. When an oxygen has a hydrogen attached, it shares its electrons unevenly. The electrons tend to hang out closer to the oxygen than to the hydrogen, so that there is a slight imbalance of charges.
Polar atoms. (a) Orange carbons share electrons evenly with their partners, which is why orange sidechains are nonpolar. (b) Red oxygen atoms tend to hoard electrons, leading to an uneven distribution of charges. Chemists use the Greek letter δ to show unabalanced "partial charges." (c) Blue nitrogen atoms also hoard electrons, and will draw electrons away from an attached hydrogen, giving the hydrogen a positive partial charge. (d) A polar hydrogen is most stable when shared between two polar atoms, creating a hydrogen bond between the hydrogen and a neighboring oxygen.
This imbalance of charges is a little unstable on its own, but another polar atom nearby can help out to balance the charges! This is the basis of a hydrogen bond. The hydrogen is less stable on its own, but becomes more stable when shared between two polar atoms.
In protein science, we tend to use the word “satisfaction” to talk about polar atoms. An unsatisfied polar atom does not make hydrogen bonds, and it has unstable, unbalanced charges. A polar atom is satisfied when it makes hydrogen bonds, and these charges are balanced.
Unsatisfied polar atoms in proteins
Polar satisfaction is very important in protein folding! When we look at natural protein structures, we see that nearly every polar atom is completely satisfied.
This makes sense, when we consider that a protein naturally folds into its most stable structure. There are lots of ways to fold up a protein with unsatisfied polar atoms, but these will be less stable than a fold where every polar atom is satisfied. A structure with many buried unsats might not even fold at all because polar atoms would rather make hydrogen bonds with the water in the unfolded state.
Polar satisfaction is the reason why helix and sheet structures are so common in proteins! These structures are able to satisfy the polar nitrogens and oxygens in the protein backbone.
This is also the reason that blue sidechains like to be on the outside of the protein, exposed to surrounding water! All of the blue sidechains have polar oxygens and nitrogens on them. Since water is also polar, the blue sidechains can make hydrogen bonds with the surrounding water.
It is possible for blue sidechains to fold in the core of the protein, but only if every polar atom makes hydrogen bonds.
Polar satisfaction. Helices (a) and sheets (b) are stable because they can satisfy all of the polar atoms on the protein backbone. (c) Blue sidechains like to be on the protein surface, but can be buried if they satisfy all of their polar atoms. This buried ARG makes 5 hydrogen bonds to satisfy all of its polar atoms.
This is especially important to remember in protein design! Sometimes a blue sidechain seems to fit really well in the protein core, even though it fails to make enough hydrogen bond to be satisfied.
It can be difficult to keep track of all the polar atoms that need to make hydrogen bonds in a protein. Unsatisfied polar atoms are one of the main reasons that Foldit player designs fail computational analysis before lab testing. We often see amazing protein designs from Foldit players that look very promising—except for one or two buried polar atoms that can’t make hydrogen bonds.
The Buried Unsats Objective
The Buried Unsats Objective detects unsatisfied polar atoms in a Foldit solution. It only detects polar atoms in the protein core, and ignores polar atoms on the protein surface (because these can make hydrogen bonds with the surrounding water).
Solutions with zero Buried Unsats get a score bonus; the bonus decreases with the number of buried polar atoms in a solution. In the Objectives panel, click ‘Show’ to highlight all of the unsatisfied polar atoms in your solution.
Polar atoms with an unbalanced hydrogen will glow blue; polar atoms that can help out will glow red. Match a blue- with a red-glowing atom to create a hydrogen bond and satisfy the polar atoms!
Some polar atoms are attached to multiple hydrogens that need to be satisfied with hydrogen bonds. When you click ‘Show’, the Buried Unsats Objective will change some of your View Settings to display all sidechains and bondable hydrogens. You can reset these options in the View tab.neilpg628 118 702 | Fri, 03/13/2020 - 01:44 | 2 comments )