Effective harmonic approach to helix proteins.

摘要

Recent laser-induced experiments have shown that on the time scale of long range tertiary contact formation, the kinetics of the helix-coil interconversion are very rapid (1). The notion that secondary structures form first before long range tertiary contacts are made, suggests that the helix-coil interconversion is one key in understanding the protein folding problem. We developed a method of generating an alpha-helix conformation of any residue using AMBER 4.0, the Protein Data Bank (PDB), and a series of pattern matching translation and rotation operations. We have chosen to study Alanine for its highly non polar nature, and Glutamine for its highly polar characteristic. Using the information obtained from the above method, analysis of vibrational lattice dynamics are carried out on polymers Poly-alpha-L alanine (PLA) and Poly-alpha-L glutamic acid (PLGA).; The lattice dynamics method called Modified Self-consistent Harmonic Approach theory (MSHA) was used in carrying out the analysis of the PLA and PLGA helix-coil transition. MSHA was originally developed for the DNA molecule by Prohofsky et al. In this model, the molecule is considered as a one dimensional, repeating unit cell of an infinite helix. The lattice was modeled with harmonic force constants. Anharmonicity of hydrogen bond force constants at different temperatures are introduced along with the effects of water on the polar PLGA and the non polar PLA.; Using MSHA, we calculated the opening bond probabilities of PLGA at different temperatures. The experimentally observed helix to coil relaxation time {dollar}tau*{dollar} of PLGA was inversely compared to our results with a correlation coefficient of 0.8424 (5, 13, 58). These experiments were done at temperatures ranging from 295 K to 310 K. Our calculation also yielded critical melting temperatures of {dollar}Tsb{lcub}c{rcub}=317{dollar} K for PLGA and {dollar}Tsb{lcub}c{rcub}=347{dollar} K for PLA. The calculated acoustic compressional velocities were 4.78 km/s and 4.84 km/s for PLA and PLGA respectively. Our calculation clearly indicates that the MSHA methodology, along with the use of AMBER 4.0, yields a good physical model of helix to coil transition of proteins.