From sequence to function: Bridging single-molecule kinetics and molecular diversity

Area of Science:

• Molecular Biology
• Biophysics
• Genomics

Background:

• Biological function is dictated by nucleic acid and protein sequences.
• Nucleic acids possess physicochemical properties influencing structure, dynamics, and interactions.
• Understanding sequence-property relationships requires methods capturing molecular diversity and dynamics.

Purpose of the Study:

• To explore advanced single-molecule techniques for analyzing molecular dynamics at scale.
• To bridge the gap between molecular sequence, structure, dynamics, and biological function.

Main Methods:

• Utilizing highly multiplexed single-molecule approaches.
• Observing molecular dynamics across millions of individual molecules and thousands of sequences.
• Developing scalable methods for analyzing sequence-dependent energetic landscapes.

Main Results:

• Demonstrated ability to observe molecular dynamics across a vast number of molecules and sequences.
• Initiated the integration of sequence, structure, dynamics, and function analysis at scale.
• Showcased the potential of these advanced techniques in various biological applications.

Conclusions:

• Highly multiplexed single-molecule methods are revolutionizing the study of sequence-function relationships.
• These techniques offer unprecedented opportunities for drug discovery, molecular diagnostics, and functional genomics.
• Ongoing development promises further advancements in understanding molecular behavior at scale.