Computer simulations of globular protein folding and tertiary structure

Area of Science:

• Computational Biology
• Structural Bioinformatics
• Protein Folding

Background:

• Predicting the three-dimensional (tertiary) structure of globular proteins from their amino acid sequences is a fundamental problem in molecular biology.
• Numerous computational techniques have been developed, but a general solution remains elusive.

Purpose of the Study:

• To review the current state of computational methods for predicting globular protein tertiary structure.
• To identify limitations and suggest future directions for solving the protein folding problem.

Main Methods:

• Review of various computational approaches, including those using detailed potentials and lattice representations.
• Analysis of the scalability of different methods with increasing protein size (residue count).
• Exploration of Monte Carlo procedures for efficient simulation.

Main Results:

• Methods predicting the conformation of small, constrained protein fragments show success.
• Detailed potential approaches are currently limited to simulating proteins of approximately 30-40 residues.
• Lattice representations combined with efficient Monte Carlo methods show promise for reducing computational complexity.

Conclusions:

• Significant theoretical advances have been made in the computer simulation of globular protein structure.
• Overcoming the limitations of current methods requires reducing the effective degrees of freedom in simulations.
• The complete globular protein folding problem is not yet solved and requires further research and development.