Correlation between the conformation space and the sequence space of Peptide chain

Area of Science:

• Computational biology
• Molecular modeling
• Protein sequence analysis

Background:

• Understanding how protein sequences evolve and maintain function is crucial.
• Point mutations can alter protein structure and function.
• Sequence selection is often driven by functional requirements.

Purpose of the Study:

• To investigate the impact of point mutations on sequence selection using a computer model.
• To explore the relationship between functional ability, conformational stability, and sequence tolerance to mutations.

Main Methods:

• Development of a computer model simulating sequence selection based on active site configuration.
• Analysis of how functional selection influences global conformation and mutation tolerance.
• Correlation analysis between conformational fluctuation and sequence fluctuation.

Main Results:

• Sequences selected for functional ability at the active site can fold into unique global conformations.
• Selected sequences exhibit tolerance to a significant number of point mutations, which are effectively neutral.
• A positive correlation exists between the structural fluctuation at specific sites and the variety of accepted point mutations.

Conclusions:

• Functional selection can lead to robust protein sequences that tolerate neutral mutations.
• Conformational flexibility at certain sites is linked to sequence flexibility and adaptability.
• The study provides insights into the evolutionary mechanisms of protein sequence diversification.