GARD: a Generally Applicable Replacement for RMSD.
The root-mean-squared deviation (rmsd) is a widely used measure of distance between two aligned objects -- often chemical structures. However, rmsd has a number of known limitations including difficulty of interpretation, no limit on weighting for any portion of the alignment, and a lack of normalization. In this work, a Generally Applicable Replacement for rmsD (GARD) is proposed. In this implementation atomic contributions are weighted by their relative importance to binding, as determined statistically by Andrews et al. (1) , and as such this method is 'chemically aware'. This novel measure is normalized and does not have many of the failings of traditional rmsd. It is, thus, perfectly suited for a wide variety of uses, including the assessment of the quality of poses produced from molecular docking programs and the comparison of conformers. Rmsd and GARD are compared in their ability to assess docking software and multiple examples of the use of GARD to rescue essentially correct poses with a high rmsd are presented.
Baber
J Christian
JC
Chemical Sciences, Wyeth Research, Cambridge, MA 02140, USA. baberj@wyeth.com
Thompson
David C
DC
Cross
Jason B
JB
Humblet
Christine
C
D000465:Algorithms; D000818:Animals; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism; D005982:Glutathione Transferase / Q000737:chemistry / Q000378:metabolism; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D009439:Neuraminidase / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D014758:Viral Core Proteins / Q000737:chemistry / Q000378:metabolism
D008024:Ligands; D011506:Proteins; D014758:Viral Core Proteins; D005982:Glutathione Transferase; D066246:ErbB Receptors; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D009439:Neuraminidase; D016333:HIV Protease