In the race to develop breakthrough therapeutics, understanding the role of water energetics can contribute novel insights to unlock new design strategies. Water molecules in and around protein binding sites are not just passive bystanders—they play an active role in molecular recognition and can influence ligand binding affinity, selectivity, and stability. Incorporating explicit water energetics into your hit discovery, docking, and lead optimization workflows provides a more nuanced view of protein-ligand interactions, helping you to predict binding outcomes more accurately and identify new opportunities to optimize leads.

This webinar will discuss the impact of two technologies that leverage explicit water energetics in the binding pocket to enhance drug design—WaterMap and Glide WS. Through evaluation of the thermodynamics of water sites, WaterMap targets high-energy, unstable hydration sites to improve the identification of better hits and more potent leads. Glide WS is a molecular docking tool that uses detailed water analysis from WaterMap calculations to evaluate the impact of desolvation events on protein-ligand binding. The combination of WaterMap and Glide WS empowers accurate pose prediction and enhances early enrichment in modern virtual screens.

We will demonstrate the impact of water energetics through Schrödinger’s collaborative SARS-CoV-2 project that led to the rapid discovery of lead compounds with unique SAR that exhibited potent enzymatic and cellular activity with excellent pan-coronavirus coverage.

Webinar Highlights

• Overview of the role of water molecules in protein binding sites and their impact on ligand docking outcomes
• How modeling explicit water energetics can uncover new binding modes and reduce false positives
• Lead optimization insights using hydration patterns to boost selectivity and drug-like properties
• Success stories from Schrödinger’s drug discovery projects