Recent trends and applications in 3D virtual screening.

Area of Science:

• Computational chemistry
• Drug discovery
• Bioinformatics

Background:

• Virtual screening (VS) is a key method in early-stage drug discovery for identifying biologically active molecules.
• In silico screening offers speed and cost-efficiency compared to traditional high-throughput screening.
• The field is evolving with advancements in three-dimensional (3D) receptor-based and ligand-based VS.

Purpose of the Study:

• To review recent trends and developments in 3D VS methodologies.
• To discuss the exploration of accessible chemical space and novel VS approaches.
• To highlight the importance of integrating complementary strategies in drug discovery.

Main Methods:

• Exploration of accessible chemical space.
• Description of 3D structural ligand-based VS techniques and hybrid approaches.
• Utilizing chemogenomic databases for enhanced VS.

Main Results:

• Discussion of challenges including pharmacokinetics, toxicity, target validation, and drug repurposing.
• Case studies on LXR-β receptor and CCR5/CXCR4 HIV co-receptors demonstrate integrated VS strategies.
• Proposed advancement through integration of complementary VS strategies.

Conclusions:

• Integrating diverse computational strategies within a single drug discovery pipeline is crucial for advancing 3D VS.
• Focusing solely on individual technique improvements is less effective than a holistic approach.
• The presented case studies exemplify the successful application of integrated VS methods.