Journal
BIOPHYSICAL CHEMISTRY
Volume 211, Issue -, Pages 28-38Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bpc.2016.01.003
Keywords
Binding pathway; Potential of mean force; Protein-ligand interaction; Michaelis-menten kinetics; Steered molecular dynamics; Jarzynski equality
Funding
- National Natural Science Foundation of China [21074115, 21273200]
- MOE [J20091551, 20090101110013]
- Zhejiang University [2011XZZX002, 2011QNA3014]
- Guangbiao Scholars program
- ARO [56781-LS]
- NSF [0958311]
Ask authors/readers for more resources
The binding free energy of 4-bromophenol (4-BP), an inhibitor that binds in the internal binding site in dehaloperoxidase-hemoglobin (DHP) was calculated using Molecular Dynamics (MD) methods combined with pulling or umbrella sampling. The effects of systematic changes in the pulling speed, pulling force constant and restraint force constant on the calculated potential of mean force (PMF) are presented in this study. The PMFs calculated using steered molecular dynamics (SMD) were validated by umbrella sampling (US) in the strongly restrained regime. A series of restraint force constants ranging from 1000 down to 5 kJ/(mol nm(2)) were used in SMD simulations. This range was validated using US, however noting that weaker restraints give rise to a broader sampling of configurations. This comparison was further tested by a pulling simulation conducted without any restraints, which was observed to have a value closest to the experimentally measured free energy for binding of 4-BP to DHP based on ultraviolet-visible (UV-vis) and resonance Raman spectroscopies. The protein-inhibitor system is well suited for fundamental study of free energy calculations because the DHP protein is relatively small and the inhibitor is quite rigid. Simulation configuration structures are compared to the X-ray crystallography structures of the binding site of 4-BP in the distal pocket above the heme. (C) 2016 Elsevier B.V. All rights reserved.
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