Comprehensive Peptide Ion Structure Studies Using Ion Mobility Techniques: Part 1. An Advanced Protocol for Molecular...

Area of Science:

• Analytical Chemistry
• Computational Chemistry
• Biophysical Chemistry

Background:

• Collision cross-section (CCS) measurements provide insights into gas-phase ion structures.
• Understanding peptide conformers is crucial for deciphering their function.
• Previous CCS calculation methods have limitations in conformational sampling.

Purpose of the Study:

• To develop advanced protocols for generating diverse in-silico peptide structures.
• To improve the accuracy of collision cross-section calculations for gas-phase conformers.
• To identify a comprehensive set of candidate structures for a model peptide.

Main Methods:

• Utilized linear drift tube for CCS measurements of a model peptide (acetyl-PAAAAKAAAAKAAAAKAAAAK).
• Employed extensive molecular dynamics (MD) simulations for unbiased conformational space sampling.
• Developed a novel CCS calculation method using clustering and data mining techniques.

Main Results:

• Generated a comprehensive pool of over 300 in-silico peptide structures with significant variations.
• MD simulations at 300 K accurately described gas-phase transport properties and dynamics.
• Proposed a new CCS calculation method demonstrating improved accuracy and conformer diversity.

Conclusions:

• Demonstrated the necessity of increased conformer diversity and accurate CCS calculations.
• The proposed advanced methods provide a robust framework for analyzing peptide conformers.
• Further studies will integrate hydrogen-deuterium exchange data to refine structural assignments and population distributions.