Finite Temperature String Method with Umbrella Sampling: Application on a Side Chain Flipping in Mhp1 Transporter
Hyun Deok Song1, Fangqiang Zhu1
1Department of Physics, Indiana University - Purdue University Indianapolis , Indianapolis, Indiana 46202, United States.
The Journal of Physical Chemistry. B
|December 14, 2016
Summary
Computational methods can now efficiently characterize protein conformational changes. This study refines transition pathways and calculates free energy landscapes for protein dynamics, aiding in understanding molecular biology.
Area of Science:
- Molecular Biology
- Computational Biophysics
Background:
- Protein conformational changes are crucial for molecular biology functions.
- Characterizing transitions between protein states is computationally challenging.
Purpose of the Study:
- To develop and apply a computational method for characterizing transitions between protein metastable conformations.
- To compute free energy landscapes and transition rates for protein dynamics.
Main Methods:
- Utilized a finite temperature string method, generalizing umbrella sampling with Hamiltonian replica exchange.
- Represented transition pathways as curves in conformational space, using reaction coordinates.
- Employed a diffusion model to calculate forward and backward transition rates.
Main Results:
- Successfully refined a transition pathway and computed a one-dimensional free energy profile.
- Applied the method to a local transition in the Mhp1 transporter.
- Predicted a 6.5 kcal/mol higher free energy for the flipped-out Phe305 side chain conformation.
Conclusions:
- The developed computational approach efficiently characterizes protein conformational transitions.
- Transition rates for the Mhp1 transporter were predicted to be in the millisecond and submicrosecond timescales.
- This method provides valuable insights into protein dynamics and kinetics.
