Player Exploration Patterns in Interactive Molecular Docking with Electrostatic Visual Cues

Serious games rely on sensory cues from the system of interest to guide players in performing a specific task. For instance, a serious game used in research and education is interactive molecular docking, where players try to bind a small molecule (ligand) to a protein (receptor) exploring the high-dimensional space of possible molecular conformations. Players are guided by a score that depends on how strongly the two molecules attract or repel each other, and by visual inspection of the three-dimensional protein surface in search of cavities where the ligand may fit. In addition, some interactive molecular docking games can also display molecules according to the charge distribution on their surface, where positively and negatively charged regions are shown in different colors. It is assumed that this color scheme helps players, since attraction and repulsion of charges contribute to the electrostatic energy between the molecules, and thus the score. In this paper we test whether adding charge information as a visual cue contributes to higher scores and exploration of more favorable energy states. For two distinct sets of ligand-receptor pairs, to test our hypothesis we compare two models: One in which players have no electrostatic information, and the other where electrostatic colors are displayed, and players are told to match parts of the molecules that may attract each other based on their colors. We collect player data and cluster energy values into states, which are treated as Markov states. Transitions between states are interpreted as players making significant changes to the score and position of the molecules, with observation of different transition probabilities corresponding to distinct exploration patterns between the two models.