Foldit drug design introduction

[jeff101]

Often single bonds - and : are used interchangeably.
Also, double bonds = and :: are user interchangeably.
Triple bonds would have ::: (6 dots).
These are because each covalent bond holds 2 electrons (2 dots).

Lone pairs contain 2 dots. For example, in NH3:

 H
 |
:N-H
 |
 H

the N has one lone pair. Also, in H2O:

 H
 |
:O:
 |
 H

the O has 2 lone pairs. The lone pairs occupy space, so they distort the geometry, making NH3 trigonal pyramidal and H2O bent.

http://www.chem.ucla.edu/harding/lewisdots.html gives some other examples.

The dots matter more when things take on free radical properties (like paramagnetism).

[free_radical]

Hi Guys,

Sorry for the delay in response. I have been working on trying to get Foldit to build for Windows using a different compiling system. We are doing this in order to get some of the code from the BCL into Foldit for windows users.

@Susume, @mottiger and @BRUNO
I am a notoriously bad speller and constantly make mistakes with acronyms. I remember when I was in first grade, I failed a spelling exam because I couldn't spell the word 'spell'. I have lab members and Nova check my work, but some things still escape :D

@BRUNO, @spmm
Currently, we are just using the new atom types for describing the configuration of atoms algorithmically. This is really important because, like shown in the figures above, ligands can have a wide variety of configurations that are not described with the Rosetta atom types. In the future, we do plan to add partial orbital charges to the new atoms, but scoring functions are really tricky. As everyone who has lived through the switch in Foldit from the original Rosetta score12 score function to the new talaris2013 score function can attest to this fact. The way we score the configurations will be with the Foldit score function, but the orientation will be described by the atom types. Spmm hits on an interesting point with wiggling the small molecule. Next week there will be a blog post on how we implemented the wiggle moves!

@LociOiling
Hybridization of orbitals help describe the 3D space occupied by the atoms and bonds between the atoms. There is a lot of chemistry and mathematics that goes into this definition, but the easiest way to describe it is that electrons are repulsive in nature. They like to be the furthest away from each other. When they interact with other electrons they form hybridizations. Its some really cool stuff!

@Bletchley Park
The algorithms that we are implementing should not require more powerful computers than what you run currently with Foldit. We are very conscious of the fact that people do not have sicentific computers, so we have modified some of our algorithms to run faster. In fact, the original implementation we made for wiggle with small molecules was changed. It was too slow and we wanted to make sure it ran on all computers, so we implemented a real cool algorithm to make it faster (for small molecules, compared to our first attempt). The models will remain around the same size and complexity, but I would be willing to put larger puzzles up if everyone wanted them. I have been in school more than 85% of my life, so I havent had any money to upgrade my computer system :( All I can recommend is to buy refurbished because its cheaper :D

@jeff101
We are playing around with the best way to go about allowing for design. There will be a long blog post about this in the upcoming weeks, but what I can say now is that there will most likely bee a free design and a reaction based design option. Free design will let you design the small molecule however you want while reaction based will require you to follow a set of synthetic reactions in order to make the small molecule. Like I said, this is all developing now, and I should have a cool blog post with graphics on this soon!