Number of possible fragments for the connectivity-based hierarchy scheme

Faithful readers of this blog (hi, mom!) will know that we have been working with the connectivity-based hierarchy (CBH) approach for a while (paper almost done). The method works by breaking molecules up into fragments and truncating with hydrogens. In the CBH-1 scheme you fragment into bonds (so propane would be fragmented into 2 ethane molecules) and in the CBH-2 scheme you include all bonds to an atom with 2 or more bonds (butane would be fragmented into 2 propane molecules).

I started wondering how many different fragments we would need to cover most organic molecules wth the CBH-2 scheme so I wrote some code (shown below) to find out and the number turns out to be 15,670 neutral molecules using ["C","N","O","F","Si","P","S","Cl","Br","I"]

This number also includes CBH-1 fragments because you need them in the CBH-2 scheme. There are a few special cases missing such as isocyanide and there aren't any rings such as cyclopropane, since these are not made until you get higher up in the CBH hierarchy.  Also, there are some very weird molecules that you'll probably never see as a functional group in an organic molecule.

The code considers all possible combinations (so it runs for a long time) and then uses RDKit to figure out if it's a reasonable molecule.

As mentioned the code only generates neutral molecules, so the actual number of fragments needed will be higher.


This work is licensed under a Creative Commons Attribution 3.0 Unported License.

New paper: Mapping Enzymatic Catalysis using the Effective Fragment Molecular Orbital Method: Towards all ab initio Biochemistry

+Casper Steinmann recently submitted the paper to PLoS ONE and is awaiting announcement on arXiv.org where you can view the manuscript.

This is the first time that a fragment based method has been applied to map out a trajectory of an enzyme - on this case the very popular chorismate mutase.

Abstract
We extend the Effective Fragment Molecular Orbital (EFMO) method to the frozen domain approach where only the geometry of an active part is optimized, while the many-body polarization effects are considered for the whole system. The new approach efficiently mapped out the entire reaction path of chorismate mutase in less than four days using 80 cores on 20 nodes, where the whole system containing 2398 atoms is treated in the ab initio fashion without using any force fields. The reaction path is constructed automatically with the only assumption of defining the reaction coordinate a priori. We determine the reaction barrier of chorismate mutase to be 18.3 +/- 3.6$ kcal mol-1 using ONIOM with MP2/cc-pVDZ and EFMO/6-31G(d) for the high and low layers, respectively.

sidenote and totally off topic: you can now reference peoples Google+ profiles directly in blogger in the same way that you do on Google+. Nicely done.

FragIt paper is out

The FragIt paper is out!

Development is ongoing but get the latest version here or give it a spin on a small protein on our online version (we are getting a larger computer so you can fragment larger molecules online)

New paper: FragIt; A Tool to Prepare Input Files for Fragment Based Quantum Chemical Calculations

Casper very recently submitted this paper to PLoS ONE and deposited it at arxiv.org

The use of fragmentation methods to treat very large systems is currently somewhat troublesome due to the complexity of the input files these programs require. We've made a tool called FragIt to generate run-ready input files which lowers the barrier of entry into this fragmented world.

Abstract
Near linear scaling fragment based quantum chemical calculations are becoming increasingly popular for treating large systems with high accuracy and is an active field of research. However, it remains difficult to set up these calculations without expert knowledge. To facilitate the use of such methods, software tools need to be available for support, setup and lower the barrier of entry for usage by non-experts. We present a fragmentation methodology and accompanying tools called FragIt to help setup these calculations. It uses the SMARTS language to find chemically appropriate substructures in structures and is used to prepare input files for the fragment molecular orbital method in the GAMESS program package. We present patterns of fragmentation for proteins and polysaccharides, specifically D-galactopyranose for use in cyclodextrins.


The source code is available at github. You can also try out a web-version at www.fragit.org.