[Babcock_Hall]

Good morning,

We are about to synthesize a potential inactivator that is intended to bind covalently to an active site cysteine.  Several structures of this enzyme have been published.  Naturally we are interested in making an inhibitor that interacts favorably with side-chains at the active site via electrostatics, H-bonding, etc.  There are several inactivators that we can synthesize, all bearing the same warhead.  Suppose we assume that a covalent bond forms.  Is Autodock a good program for us to use in answering these questions?  As I see it, we would be trying to see what conformation the inhibitor takes when covalently linked to the enzyme.  I don't know enough about molecular modeling programs to answer these sorts of questions.

[curiouscat]

Very interesting question. Too bad you didn't get an answer. I'd love to hear too.

I'm no expert on this but as a program have you explored the Accelrys Suite of Products? I thought they too had some good programs to do this.

PS. Made any progress on this on your own? Would love to hear what.

[Yggdrasil]

Try taking a look at the work of Brian Shoichet, for example: http://www.ncbi.nlm.nih.gov/pubmed/25344815

[Babcock_Hall]

curiouscat, We have not made much progress, but we are still plugging away.

Yggdrasil,  I am slightly acquainted with Brian Shoichet, and he is a very nice person.  Thank you for the reference; I will have to read his paper this weekend.

[Babcock_Hall]

http://covalent.docking.org

This is a web-based tool from UCSF.  We are running low on time with respect to the semester, but it is nice to know for the future that someone has gotten as far along as this.