Root Mean Squared Deviation (RMSD) is a commonly used feature for comparing different conformations of given molecular systems. In Molecular Dynamics (MD) and Protein-ligand Docking (PLD) approaches, for example, this measure is essential to the analysis and validation of the results. In the case of PLD, RMSD is routinely utilized to measure the quality of reproduction of a known binding pose by comparing the obtained ligand pose with experimental crystallographic source. For this, components might show a full atomic equivalence. Most methods available for RMSD calculations assume an equivalence between the atoms of the molecules, requiring uniquely the atom indices for the measures. Unfortunately, the vast majority of the 3D molecule files are generated using strategies of random atom labeling and rarely consider the possible symmetry of certain types of atoms or fragments (Coutsias and Wester,2019. Thus, to avoid inaccurate RMSD values, it is necessary previous identification and matching of equivalent elements (atoms, bonds, etc) between the docked compound and its reference.
Tools such as pyRMSD ( Gil and Guallar, 2013), VMD (Humphrey et al., 1996), Gromacs (Berendsen et al., 1995), among others, can accurately measure RMSD between two identical chemical compounds whose equivalent atoms were previously identified; however, this pre-processing step can be in some cases a very time-demanding task. Moreover, to avoid this problem (but with a high computational cost), some tools perform multiple RMSD calculations using several permutations/combinations of atom labels between a pair of molecules, selecting at the end of measures, the lowest RMSD obtained (Temelso et al., 2017)
RMSD calculations between compounds from a database and a reference compound (comparison between similar compounds) are less used. When compounds share partially their structures it is possible to determine which atoms are common between the compared structures, typically referred to as the maximum common substructure (MCS; Cao Y et al., 2008). Some available resources such as Pymol (DeLano W.L. ,2002), Maestro (Schrödinger LLC., 2018) and RDKit libraries (Landrum, 2018), partially deal with this kind of problems, including the finding of the MCS between different compounds. Nevertheless, the use of these tools still requires additional file manipulations and therefore, new approaches that allow the automatics matching, renaming, and calculation of the RMSD value between any pair (or database) of chemical compounds are currently necessary.
Here, we present LigRMSD, a free web-server for the automatic matching and RMSD calculations among identical or similar chemical compounds. The core of LigRMSD was written in python language, and some critical libraries of RDkit were implemented. The interface of the web-server is highly intuitive, allowing the user to obtain the RMSD for two cases; between a pair of molecules or against a database. Remarkably, all the calculations are done without any users file manipulation required.
DOI: https://doi.org/10.1093/bioinformatics/btaa018
If you have any question about LigRMSD, please send us an email to ganunez@utalca.cl or jcaballero@utalca.cl