Quantifying the Kinetic Residence Time as a Potential Complement to Affinity for the Aptamer Selection.

Area of Science:

• Biotechnology
• Computational Biology
• Molecular Biophysics

Background:

• Aptamers are increasingly used in biotechnology and therapeutics.
• Aptamer quality depends on thermodynamic stability and kinetic residence time.
• Current selection methods optimize only binding affinity.

Purpose of the Study:

• To propose a computational method for quantifying aptamer-target residence time.
• To evaluate residence time as a metric for aptamer quality.
• To suggest a dual selection strategy incorporating residence time.

Main Methods:

• Modeling aptamer-target binding kinetics as a diffusion process on an energy landscape.
• Quantifying residence time using the proposed computational method.
• Assessing the ability of residence time to distinguish native from non-native aptamer complexes.

Main Results:

• The computational method successfully quantifies residence time.
• Quantified residence time can discriminate native from non-native aptamer complexes.
• Residence time correlates with binding affinity but shows dispersion, indicating its complementary role.

Conclusions:

• Residence time is a crucial parameter for aptamer selection.
• A two-dimensional selection method combining binding affinity and residence time is proposed.
• This approach offers a more comprehensive strategy for aptamer development.