Intrinsically Disordered Landscapes for Human CD4 Receptor Peptide.

Area of Science:

• Biophysics
• Computational Biology
• Structural Biology

Background:

• Intrinsically disordered proteins (IDPs) possess inherent structural plasticity, complicating experimental and simulation-based characterization.
• The human CD4 receptor peptide, a disordered region, plays a role in HIV-1 infection, highlighting its importance in biological systems.

Purpose of the Study:

• To implement and test a potential energy landscape framework for studying IDPs.
• To characterize the human CD4 receptor peptide and assess the impact of different AMBER force fields on its energy landscape.

Main Methods:

• Basin-hopping parallel tempering and discrete path sampling were employed for IDP characterization.
• Three state-of-the-art AMBER force fields (ff99SB-ILDN, ff14ipq, ff14SB) were evaluated for their influence on the energy landscape.

Main Results:

• The ff99SB-ILDN force field demonstrated the best agreement with experimental data.
• Metastable states were identified on the free energy surface, aligning with and unifying previous predictions.

Conclusions:

• The potential energy landscape approach provides a viable method for characterizing IDPs like the CD4 receptor peptide.
• Identified metastable states offer potential starting points for investigating the CD4-HIV-1 interaction interface.