Force Fields, Quantum-Mechanical- and Molecular-Dynamics-Based Descriptors of Radiometal-Chelator Complexes

Area of Science:

• Radiopharmaceutical chemistry
• Computational chemistry
• Drug design

Background:

• Radiopharmaceuticals are vital for cancer diagnosis and therapy.
• Metal-based radiopharmaceuticals require careful selection of radiometal and chelator for optimal efficacy.
• Understanding radiometal-chelator interactions is key to developing new cancer drugs.

Purpose of the Study:

• To systematically investigate radiometal-chelator complexes using computational methods.
• To generate force field parameters and molecular descriptors for these complexes.
• To provide data for predictive modeling and rational drug design in radiopharmaceutical development.

Main Methods:

• Systematic investigation of ~120 radiometal-chelator complexes from the Cambridge Structural Database.
• Utilized quantum mechanics (density functional theory) for parameter generation.
• Performed 1 µs all-atom molecular dynamics simulations in explicit water.

Main Results:

• Extracted key molecular descriptors based on electronic and dynamic properties.
• Validated computational workflow and investigated selected test cases.
• Generated and made freely available force field parameters and molecular descriptors.

Conclusions:

• The study offers new insights into radiometal-chelator complex properties.
• Freely available data will facilitate predictive models and molecular dynamics studies.
• Findings directly impact the rational drug design of metal-based radiopharmaceuticals.