Empirical force field for cisplatin based on quantum dynamics data: case study of new parameterization scheme for...

Area of Science:

• Computational Chemistry
• Molecular Dynamics
• Quantum Chemistry

Background:

• Parameterizing molecular complexes with metallic elements, exemplified by cisplatin, presents challenges due to unique platinum atom coordination.
• Accurate molecular modeling requires reliable parameterization that captures the dynamic behavior of such compounds.

Purpose of the Study:

• To develop a novel methodology for parameterizing metallic compounds using quantum dynamics (QD) calculations.
• To investigate the flexibility of cisplatin and the influence of solvent on its dynamics.
• To create improved molecular dynamics (MD) topologies for organometallic compounds.

Main Methods:

• Utilized quantum dynamics (QD) calculations to parameterize cisplatin.
• Generated two empirical topologies by fitting atomic fluctuations against QD data in vacuum and with explicit solvent.
• Compared QD-based topologies with a standard topology derived from static structures.

Main Results:

• QD calculations revealed that cisplatin's coordination bonds and angles are more flexible than in typical covalent compounds.
• Explicit solvent significantly influences cisplatin's flexibility in QD simulations.
• Standard topologies result in an overly rigid cisplatin molecule, failing to capture its true flexibility.
• QD-based flexible topologies accurately describe cisplatin's hydration shell and reduce passive diffusion barriers across lipid bilayers.

Conclusions:

• The flexibility of organometallic compounds is a critical factor for accurate molecular dynamics simulations.
• The proposed QD-based methodology offers a systematic approach to generating reliable topologies for metallic compounds.
• This work enhances the understanding and simulation of cisplatin and similar molecules in biological and chemical systems.