Journal
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
Volume 7, Issue 9, Pages 2721-2727Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ct200153u
Keywords
-
Funding
- National Institute of Health [1R01AI073674]
- NSF [1047919]
- Large Allocations Resource Committee [TG-MCA05S010]
- University of Florida High-Performance Computing Center
- Direct For Computer & Info Scie & Enginr
- Office of Advanced Cyberinfrastructure (OAC) [1047919, 1047875] Funding Source: National Science Foundation
Ask authors/readers for more resources
Alchemical free energy calculations play a very important role in the field of molecular modeling. Efforts have been made to improve the accuracy and precision of those calculations. One of the efforts is to employ a Hamiltonian replica exchange molecular dynamics (H-REMD) method to enhance conformational sampling. In this paper, we demonstrated that the H-REMD method not only improves convergence in alchemical free energy calculations but also can be used to compute free energy differences directly via the Free Energy Perturbation (FEP) algorithm. We show a direct mapping between the H-REMD and the usual FEP equations, which are then used directly to compute free energies. The H-REMD alchemical free energy calculation (replica exchange free energy perturbation, REFEP) was tested on predicting the plc value of the buried Asp26 in thioredoxin. We compare the results of REFEP with TI and regular FEP simulations. REFEP calculations converged faster than those from TI and regular FEP simulations. The final predicted pK(a) value from the H-REMD simulation was also very accurate, only 0.4 pK(a) units above the experimental value. Utilizing the REFEP algorithm significantly improves conformational sampling, and this in turn improves the convergence of alchemical free energy simulations.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available