Water in drug design: pitfalls and good practices

Area of Science:

• Computational chemistry and structural biology.
• Molecular modeling and drug discovery.

Background:

• Structure-based drug design optimizes molecular interactions.
• Water significantly influences drug-target complex stability and function.
• Understanding water's complex roles is vital for successful drug design.

Purpose of the Study:

• To review the multifaceted roles of water in drug design.
• To discuss methods for determining water structure at atomic resolution.
• To explore techniques for quantifying water's impact on drug-target complexes.

Main Methods:

• Literature search of PubMed, Web of Science, and Google Scholar.
• Analysis of topographical and networking situations of water molecules.
• Discussion of computational and experimental techniques.

Main Results:

• Water's role varies greatly depending on its local environment.
• Accurate determination of water structure is key to overcoming design pitfalls.
• Computational approaches offer cost-effective solutions to experimental limitations.

Conclusions:

• Water can be transformed from a challenge into a valuable tool in drug design.
• Fine-tuning drug-target interactions is achievable with a deeper understanding of water.
• Advances in computational methods enhance the predictive power of drug design.