Optimized CGenFF force-field parameters for acylphosphate and N-phosphonosulfonimidoyl functional groups

Area of Science:

• Computational chemistry
• Molecular modeling
• Drug discovery

Background:

• Small molecules with acylphosphate and N-phosphonosulfonimidoyl functional groups are relevant in biological systems.
• Accurate molecular modeling requires well-defined force field parameters.

Purpose of the Study:

• To develop and validate optimized CGenFF parameters for acylphosphate and N-phosphonosulfonimidoyl functional groups.
• To facilitate computational studies of enzymes involved in acyladenylate intermediate metabolism.
• To support the development of novel inhibitors for glutamine-dependent amidotransferases.

Main Methods:

• Standard CGenFF procedures for bonded interaction parameters.
• Geometry optimizations and MP2/6-31+G(d) calculations for validation.
• Molecular dynamics simulations and hydrogen bonding energy analysis with water.

Main Results:

• Optimized CGenFF parameters were obtained for the specified functional groups.
• Parameters were validated against high-level quantum mechanical calculations and simulations.
• Partial atomic charges accurately reproduced hydrogen bonding energies with water.

Conclusions:

• The developed parameters enhance the CHARMM force field for modeling relevant small molecules.
• These parameters will advance computational investigations of enzyme mechanisms and drug design.
• Available topology and parameter files will aid broader research in acylphosphate and N-phosphonosulfonimidate systems.