Implicit Solvent
From wiki.gromacs.org
A repeating question on the mailing list whether GROMACS can perform implicit solvent simulations. The answer is, not really. Over the last few years there have been quite a few papers in (good) journals about why one in general should or should not us it. Please search literature by Ruhong Zhou, Vijay Pande and/or Bruce Berne on the subject (and fill in the references here plus DOI links etc.).
- R. Zhou and B. J.Berne Can a continuum solvent model reproduce the free energy landscape of a $beta$-hairpin in water?, Proc. Natl. Acad. Sci. U.S.A. 99 (2002), 12777-12782
- Young Min Rhee, Eric J. Sorin, Guha Jayachandran, Erik Lind and Vijay S. Pande, Simulations of the role of water in the protein- folding mechanism, Proc. Natl. Acad. Sci. U.S.A. 101 (2004), 6456-6461
- http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15814616
The current state in Gromacs is that we already have very optimized assembly kernels for the actual generalized born interaction, so that part is done. We also have C language functions to calculate Still radii (not yet in CVS), although these have to be ported to assembly for decent performance.
The one big remaining issue is a fast surface calculation algorithm. The problem with the commonly used ones (e.g. Still) is that everything else in Gromacs (including the GB loops) is an order of magnitude faster, so that surface calculation would take over 90% of the time. They also do not parallelize easily.
There are some tricks we can use (e.g. only calculating surface every N steps), but we still need a _very_ fast surface calculation algorithm. The best starting point in the literature is probably the algorithm of Brooks, where you simply have empiric parameters for sp2/sp3/sp neighbors of different atom types combined with a short neighborlist.
We definitely need approximate derivatives of the surface free energy w.r.t. all atom coordinates, and the last couple of years there has also been some discussion that the volume term could be even more important than the surface, so preferably volume derivatives too. If you're interested in helping I (lindahl@cbr.su.se) have reference code that calculates both surface/volume and the associated derivatives analytically.
