Intermolecular Sulfur···Oxygen Interactions: Theoretical and Statistical Investigations

Area of Science:

• Biochemistry
• Computational Chemistry
• Structural Biology

Background:

• Intermolecular sulfur-oxygen (S···O) interactions are prevalent in biological systems but often discovered serendipitously.
• Rational design of these interactions in protein-ligand systems has been limited.

Purpose of the Study:

• To elucidate the phenomenon of intermolecular S···O contacts.
• To characterize their strength, directionality, and energy dependence.
• To explore their application in molecular design for improved binding affinities and physiochemical properties.

Main Methods:

• Quantum mechanics calculations to analyze S···O interaction properties.
• Protein Data Bank mining to identify occurrence and geometry.
• Combined quantum mechanics/molecular mechanics (QM/MM) approach for case studies.

Main Results:

• Detailed characterization of S···O interaction strength and directionality.
• Systematic analysis of S···O contact occurrence and geometry in protein-ligand complexes.
• Demonstration of S···O interactions enhancing binding affinities and physiochemical properties in model systems.

Conclusions:

• Intermolecular S···O interactions possess distinct structural and energetic features.
• These interactions can be rationally exploited in molecular design.
• Further understanding can advance drug discovery and development.