MixMD Probeview: Robust Binding Site Prediction from Cosolvent Simulations

Mixed-solvent molecular dynamics
(MixMD) is a cosolvent simulation
technique for identifying binding hotspots and specific favorable
interactions on a protein’s surface. MixMD studies have the
ability to identify these biologically relevant sites by examining
the occupancy of the cosolvent over the course of the simulation.
However, previous MixMD analysis required a great deal of manual inspection
to identify relevant sites. To address this limitation, we have developed
MixMD Probeview as a plugin for the freely available, open-source
version of the molecular visualization program PyMOL. MixMD Probeview
incorporates two analysis procedures: (1) identifying and ranking
whole binding sites and (2) identifying and ranking local maxima for
each probe type. These functionalities were validated using four common
benchmark proteins, including two with both active and allosteric
sites. In addition, three different cosolvent procedures were compared
to examine the impact of including more than one cosolvent in the
simulations. For all systems tested, MixMD Probeview successfully
identified known active and allosteric sites based on the total occupancy
of neutral probe molecules. As an easy-to-use PyMOL plugin, we expect
that MixMD Probeview will facilitate identification and analysis of
binding sites from cosolvent simulations performed on a wide range
of systems.