Folding and thermodynamic studies of Trp-cage based on polarized force field

• Published in: Theoretical chemistry accounts 2012-03, Vol.131 (3), Article 1168
• Main Authors: Mei, Ye, Wei, Caiyi, Yip, Yew Mun, Ho, Chun Ying, Zhang, John Z. H., Zhang, Dawei
• Format: Article
• Language: English
• Subjects: Atomic/Molecular Structure and Spectra; Chemistry; Chemistry and Materials Science; Inorganic Chemistry; Letter; Organic Chemistry; Physical Chemistry; Theoretical and Computational Chemistry
• ISSN: 1432-881X; 1432-2234
• DOI: 10.1007/s00214-012-1168-0

Two replica exchange molecular dynamics (REMD) simulations were carried out to study the thermodynamics of a 20-residue Trp-cage folding based on a newly developed polarized protein-specific charge (PPC). Starting from a fully extended conformation, Trp-cage native conformation was successfully sampled using REMD based on a 3-step PPC update. Next, the obtained Trp-cage folded conformation was then used to calculate the PPC in which another REMD was performed to explore the thermodynamic stability of Trp-cage. The theoretical melting temperature T m of ≈325 K was found to be in close agreement with experimental melting temperature, T m of 315 K. This indicates that the PPC was correctly predicting the temperature dependence. The current study provides a direct proof of how electrostatic polarization affects protein folding.