Related Experiment Video
Updated: May 15, 2026
08:03
Study of Protein Dynamics via Neutron Spin Echo Spectroscopy
Published on: April 13, 2022
Quantum and classical dynamics simulations of ATP hydrolysis in solution
Christopher B Harrison1, Klaus Schulten
1Beckman Institute and Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Journal of Chemical Theory and Computation
|January 8, 2013
Summary
Adenosine triphosphate (ATP) hydrolysis, crucial for cellular processes, was studied using advanced QM/MM simulations. This method accurately captures solvent relaxation, revealing insights into ATP hydrolysis mechanisms and the role of Mg(2+).
Area of Science:
- Computational Chemistry
- Biochemistry
- Molecular Dynamics
Background:
- Adenosine triphosphate (ATP) hydrolysis powers cellular functions, but its reaction mechanism (associative vs. dissociative) is debated.
- Previous quantum chemical studies were limited by short timescales, neglecting solvent relaxation's free energy contributions.
- Understanding ATP hydrolysis is vital for comprehending cellular energy transduction.
Purpose of the Study:
- To develop and apply a highly parallelized QM/MM method for accurate simulation of ATP hydrolysis.
- To investigate both associative and dissociative mechanisms of ATP hydrolysis.
- To elucidate the role of Mg(2+) and solvent relaxation in the reaction free energy.
Main Methods:
- Developed a novel, highly parallelized QM/MM implementation using NAMD and OpenAtom.
- Employed a dual grid, dual length scale method for combined plane-wave and Eular exponential spline QM/MM simulations.
- Utilized message-driven parallel quantum and classical dynamics for extended simulation timescales.
Main Results:
- The QM/MM approach enabled simulations of sufficient timescale to capture quantum chemical events like ATP hydrolysis.
- The method accurately and reliably included free energy contributions from solvent relaxation.
- Both associative and dissociative mechanisms of ATP hydrolysis were studied, considering Mg(2+) and solvent effects.
Conclusions:
- The developed QM/MM method provides accurate and reliable insights into ATP hydrolysis mechanisms.
- Solvent relaxation and Mg(2+) play critical roles in the free energy landscape of ATP hydrolysis.
- This computational approach advances the study of key biochemical reactions in biological systems.
Related Concept Videos
01:08Hydrolysis of ATP
The bonds of adenosine triphosphate (ATP) can be broken through the addition of water, releasing one or two phosphate groups in an exergonic process called hydrolysis. This reaction liberates the energy in the bonds for use in the cell—for instance, to synthesize proteins from amino acids.
If one phosphate group is removed, a molecule of ADP—adenosine diphosphate—remains, along with inorganic phosphate. ADP can be further hydrolyzed to AMP—adenosine monophosphate—by the removal of a second...
If one phosphate group is removed, a molecule of ADP—adenosine diphosphate—remains, along with inorganic phosphate. ADP can be further hydrolyzed to AMP—adenosine monophosphate—by the removal of a second...
01:08Hydrolysis of ATP
The bonds of adenosine triphosphate (ATP) can be broken through the addition of water, releasing one or two phosphate groups in an exergonic process called hydrolysis. This reaction liberates the energy in the bonds for use in the cell—for instance, to synthesize proteins from amino acids.
If one phosphate group is removed, a molecule of ADP—adenosine diphosphate—remains, along with inorganic phosphate. ADP can be further hydrolyzed to AMP—adenosine monophosphate—by the removal of a second...
If one phosphate group is removed, a molecule of ADP—adenosine diphosphate—remains, along with inorganic phosphate. ADP can be further hydrolyzed to AMP—adenosine monophosphate—by the removal of a second...
01:27ATP Driven Pumps I: An Overview
ATP-driven pumps, also known as transport ATPases, are integral membrane proteins. They have binding sites for ATP located on the membrane's cytosolic side and the ion-conducting domain in the transmembrane region. These pumps use the free energy released from ATP hydrolysis to move the solutes across cell membranes against an electrochemical gradient.
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and are...
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and are...
01:48ATP Synthase: Mechanism
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
01:18ATP Synthase: Structure
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
01:30ATP Driven Pumps III: V-type Pumps
V-type pumps are ATP-driven pumps found in the vacuolar membranes of plants, yeast, endosomal and lysosomal membranes of animal cells, plasma membranes of a few specialized eukaryotic cells, and some prokaryotes. They are also known as the V1Vo-ATPase, that couple ATP hydrolysis to transport protons against a concentration gradient.
The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits...
The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits...