While I was at Accelrys one of the things that I tried to push was an increased use of force fields, MD and more physical approaches for molecular recognition problems like ligand docking. It’s always good to see some of those thoughts and early proofs-of-concept become reality
Technorati Tags: CHARMM, Ligand Docking, Flexible Docking
4 Comments
I’m not really an expert in this area, but this is not that novel is it? I’ve seen work that uses force fields for areas around the active sound, with QM of the active side, ligand and the involved receptor residues. I believe the context was reactions. How is this different?
I'm not really an expert in this area, but this is not that novel is it? I've seen work that uses force fields for areas around the active sound, with QM of the active side, ligand and the involved receptor residues. I believe the context was reactions. How is this different?
Depends. I was doing QMMM around protein active sites 10 years ago, but in the docking community with an emphasis on throughput, in general docking functions used a soft potential and a mostly rigid receptor with flexible ligands, and scoring functions were rule or knowlede based. As computers have become more powerful and with an emphasis on quality it’s become more common to use flexible receptors and higher order potentials. QM is still rare (too slow). As someone once told me, you have to be faster than the medicinal chemists
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In this case, it was more of a personal win, to get the structure-based drug design folks to start thinking of using MD-based search schemes and MM-based potentials. The above talk probably uses a modification of Charlie Brook’s CDOCKER method and a full workflow (conformer generation, etc) in Pipeline Pilot.
Depends. I was doing QMMM around protein active sites 10 years ago, but in the docking community with an emphasis on throughput, in general docking functions used a soft potential and a mostly rigid receptor with flexible ligands, and scoring functions were rule or knowlede based. As computers have become more powerful and with an emphasis on quality it's become more common to use flexible receptors and higher order potentials. QM is still rare (too slow). As someone once told me, you have to be faster than the medicinal chemists
.
In this case, it was more of a personal win, to get the structure-based drug design folks to start thinking of using MD-based search schemes and MM-based potentials. The above talk probably uses a modification of Charlie Brook's CDOCKER method and a full workflow (conformer generation, etc) in Pipeline Pilot.