The Art of FREE Molecular Docking (Using DOCK 6.1) (Part 1)

Introduction and Installation

Enzymes play an important role in living organisms. They catalyze chemical reactions, where a substrate is converted into a product. Substrates are molecules that bind into the enzyme's active site where it undergoes conversion into the enzymatic product. I am not going to go too deep regarding enzymes, since you can find similar resources for this in the Internet (Wikipedia is a good place to start off).

What I am going to talk about, is a pragmatic way to better understand the interaction between an enzyme and its substrate using molecular modeling, in this case, docking using DOCK 6.1 (check the DOCK website at: http://dock.compbio.ucsf.edu). Well, mostly, I will be talking about my experience using the program, from installation to the docking process.

So what is docking?
Substrates, as do all molecules, have many different conformations they can take. The conformations play a determining factor in the way it binds to the active site of an enzyme. What also needs to be elucidated is the binding orientation, interaction energy (Ei), etc. One way to predict the orientation, conformation, and interaction energy (Ei) of an enzyme-substrate complex, is by molecular docking using in silico (computer) analysis. In short words, docking is meant to see the interaction between molecules and ligands (enzyme or protein). In my case, the data retrieved will then be analyzed to see substrate preference of the enzyme tested.

There is a wide range of programs that can be used for molecular docking, from freeware to expensive commercial wares. Among all, GOLD and Glide are considered to have the best accuracy. But to obtain one of them, you will need to invest at least around 3.200 USD. Too expensive for a student like me, and my lab hasn't allocated that much money to buy softwares. Anyway, for the solution, I tried to search for freewares. To my surprise, I found a lot of docking freewares. Among them are ArgusLab 4.0, Autodock, and DOCK.

At first, I tried ArgusLab 4.0, which was fairly easy to use. Installation was easy (it runs on windows XP), it has a nice GUI, and accompanied with an easy step by step tutorial, I was able to complete the docking process in no time (you can check out their website: http://www.planaria-software.com). However, the software isn't yet recognized in the scientific community. A quick search using the key word “Arguslab” in google scholar only resulted in 66 hits. There is even a comparison of Arguslab with GOLD, which shows that there are many things that needs to be improved in the current Arguslab version. Thus, I moved on to the other options.

Autodock was indeed tempting, however, the procedures to obtain a copy was somewhat “difficult”. You will need to send a fax or mail with the head of your institutes' signature on the license agreement. I am studying in Japan, and it takes time to complete procedures like that. That's why I moved on to DOCK 6.1. It wasn't hard to obtain, since you only have to fill in an on line request (with permission of your supervising Professor) to get it. I got the software after 2-3 days of my request. Lighting quick response.

So, I got the software, now what? Install it right? Well, it turned out not as easy as I suspected. To install DOCK, you will need a UNIX like environment. On windows, you can use a program called CYGWIN, which generates a UNIX like environment in windows. However, I opted to install openSuse linux (which is UNIX based) on my computer (I had a double OS booting). I compared the docking performance on both (cygwin and linux), and found that it was much more stable using the later (linux). The installation itself was sort of a trial and error process. You will need to install the compilers and other programs that are required to use DOCK (check the tab “dock related links” on their website). For a tutorial on installation of DOCK, you can see the DOCK manual (you will need to improvise though). I will make my own step by step installation soon.

Finished installing, you will have all the programs that you need in the /bin/ directory of your installation directory. However, you will need another program called “dms” (to compute molecular surface), which is not included in the DOCK package (you can get dms from: ftp://ftp.cgl.ucsf.edu/pub/dms.zip). I'll give details on installing it later.

There are 4 steps in docking with DOCK, which I will mention in my next post.