Schrodinger's equation

A friend of mine just returned from a conference in New York organised by Schrodinger, and I have to say that Schrodinger really seems to be poised to be the one-stop shop for all things computational.

They already have some great programs in their Maestro suite, including Glide for docking, which you find folks in industry using more and more these days. In their next revisions, they are going to introduce a program named PrimeX for doing crystallography, which will perform analysis similar to CNS, which will be groovy if it brings such analysis to the desktop. They are also going to introduce electron-density fitting for loop refinement in proteins. Right now, loop refinement of, say a 10 residue loop takes forever. But with PrimeX and friends, one can have constraints effected by electron density to restrict conformational searching, thus greatly speeding up the process.

Other products include the very impressive new Glide XP docking protocol. I have been glued to their site ever since they published their admirable paper in 2006. I have already written about the capabilities of GlideXP. This is really the best of computational chemistry applied to docking, where you find chemists trying to include as many experimental parameters as they can in a program. Schrodinger is definitely one company whose chemists have a firm and steady hand on experimental variables.

A very important development is going to be the interfacing of William Jorgensen's MCPRO, a program for doing free energy perturbation (FEP) calculations. FEP calculations are as close as you can come to accurately reproducing experimental binding free energies, one of the holy grails of computational methodology. While GlideXP astoundingly claims to also be able to do that, it would be super to have a GUI and easy operability for a good FEP program at your fingertips. Admittedly, FEP works only for ligand which differ little in their structure (eg. Me vs H). But that's also the phenomenon which we understand the least, how "similar" ligands can have great differences in binding affinity, something which FEP should help us understand.

Other improvements will include better parameters in standard docking, and a new force field, OPLS 2008, which will be "better than MMFF". Considering that the force behind this field is Tom Halgren, the same guy who meticulously crafted MMFF, I would be looking forward to it. There is also talk of a new MD program comparable to Gromacs, AMBER etc. which can do millisecond MD efficiently. That would probably complete the list of capabilities in one program that almost any computational chemist could want.

What I like best about Schrodinger is that it has people at its helm who are among the best that computational chemistry has to offer, most importantly Richard Friesner and Tom Halgren. Looking at their papers, it's clear that like ideal computational chemists, they thoroughly understand experimental data, and clearly know what the limitations of their programs are.