Biomedical subjects

Yi Qin Gao

Publications and source records attributed to Yi Qin Gao.

7 recordsLinked to original sources

PubMed2006

On the enhanced sampling over energy barriers in molecular dynamics simulations.

We present here calculations of free energies of multidimensional systems using an efficient sampling method. The method uses a transformed potential energy surface, which allows an efficient sampling of both low and high energy spaces and accelerates transitions over barriers. It allows efficient sampling of the configuration space over and only over the desired energy range(s). It does not require predetermined or selected reaction coordinate(s). We apply this method to study the dynamics of slow barrier crossing processes in a disaccharide and a dipeptide system.

Journal Article↗

PubMed2006

On the hand-over-hand mechanism of kinesin.

We present here a simple theoretical model for conventional kinesin. The model reproduces the hand-over-hand mechanism for kinesin walking to the plus end of a microtubule. A large hindering force induces kinesin to walk slowly to the minus end, again by a hand-over-hand mechanism. Good agreement is obtained between the calculated and experimental results on the external force dependence of the walking speed, the forward/backward step ratio, and dwell times for both forward and backward steps. The model predicts that both forward and backward motions of kinesin take place at the same chemical state of the motor heads, with the front head being occupied by an ATP (or ADP,Pi) and the rear being occupied by an ADP. The direction of motion is a result of the competition between the power stroke produced by the front head and the external load. The other predictions include the external force dependence of the chemomechanical coupling ratio (e.g., the stepping distance/ATP ratio) and the walking speed of kinesin at force ranges that have not been tested by experiments. The model predicts that the chemomechanical coupling remains tight in a large force range. However, when the external force is very large (e.g., approximately 18 pN), kinesin slides in an inchworm fashion, and the translocation of kinesin becomes loosely coupled to ATP turnovers.

Adenosine Diphosphate↗

PubMed2005

A simple theoretical model explains dynein's response to load.

Recent experiment showed that cytoplasmic dynein 1, a molecular motor responsible for cargo transport in cells, functions as a gear in response to external load. In the presence of vanishing or small external load, dynein walks with 24- or 32-nm steps, whereas at high external load, its step size is reduced to 8 nm. A simple model is proposed to account for this property of dynein. The model assumes that the chemical energy of ATP hydrolysis is used through a loose coupling between the chemical reaction and the translocation of dynein along microtubule. This loose chemomechanical coupling is represented by the loosely coupled motions of dynein along two different reaction coordinates. The first reaction coordinate is tightly coupled to the chemical reaction and describes the protein conformational changes that control the chemical processes, including ATP binding and hydrolysis, and ADP-Pi release. The second coordinate describes the translocation of dynein along microtubule, which is directly subject to the influence of the external load. The model is used to explain the experimental data on the external force dependence of the dynein step size as well as the ATP concentration dependence of the stall force. A number of predictions, such as the external force dependence of speed of translocation, ATP hydrolysis rate, and dynein step sizes, are made based on this theoretical model. This model provides a simple understanding on how a variable chemomechanical coupling ratio can be achieved and used to optimize the biological function of dynein.

Adenosine Diphosphate↗

PubMed2005

A structure-based model for the synthesis and hydrolysis of ATP by F1-ATPase.

Many essential functions of living cells are performed by nanoscale protein motors. The best characterized of these is F(o)F1-ATP synthase, the smallest rotary motor. This rotary motor catalyzes the synthesis of ATP with high efficiency under conditions where the reactants (ADP, H2PO4(-)) and the product (ATP) are present in the cell at similar concentrations. We present a detailed structure-based kinetic model for the mechanism of action of F1-ATPase and demonstrate the role of different protein conformations for substrate binding during ATP synthesis and ATP hydrolysis. The model shows that the pathway for ATP hydrolysis is not simply the pathway for ATP synthesis in reverse. The findings of the model also explain why the cellular concentration of ATP does not inhibit ATP synthesis.

Adenosine Triphosphate↗

PubMed2005

Protein structural transitions and their functional role.

Living cells are a collection of molecular machines which carry out many of the functions essential for the cell's existence, differentiation and reproduction. Most, though not all, of these machines are made up of proteins. Because of their complexity, an understanding of how they work requires a synergistic combination of experimental and theoretical studies. In this paper we outline our studies of two such protein machines. One is GroEL, the chaperone from Escherichia coli, which aids in protein folding; the other is F(1)-ATPase, a motor protein which synthesizes and hydrolyses ATP.

Chaperonin 60↗

PubMed2004

Biomolecular motors: the F1-ATPase paradigm.

The realization that many essential functions of living cells are performed by nanoscale motors consisting of protein complexes has given rise to an intense effort to understand their mechanisms. Considerable progress has been made in the past two years by a combination of biophysical techniques and theoretical analysis. Single-molecule studies have played a spectacular role for a variety of motors including kinesin, myosin, and polymerases. The understanding of F(1)-ATPase, the smallest biomolecular rotary motor, has made particular progress by the interplay of experimental and theoretical studies; the latter have provided information not available from experiment.

Animals↗

PubMed2003

A model for the cooperative free energy transduction and kinetics of ATP hydrolysis by F1-ATPase.

Although the binding change mechanism of rotary catalysis by which F1-ATPase hydrolyzes ATP has been supported by equilibrium, kinetic, and structural observations, many questions concerning the function remain unanswered. Because of the importance of this enzyme, the search for a full understanding of its mechanism is a key problem in structural biology. Making use of the results of free energy simulations and experimental binding constant measurements, a model is developed for the free energy change during the hydrolysis cycle. This model makes possible the development of a kinetic scheme for ATP hydrolysis by F1-ATPase, in which the rate constants are associated with specific configurations of the beta subunits. An essential new element is that the strong binding site for ADP,Pi is shown to be the betaDP site, in contrast to the strong binding site for ATP, which is betaTP. This result provides a rationale for the rotation of the gamma subunit, which induces the cooperativity required for a tri-site binding change mechanism. The model explains a series of experimental data, including the ATP concentration dependence of the rate of hydrolysis and catalytic site occupation for both the Escherichia coli F1-ATPase (EcF1) and Thermophilic Bacillus PS3 F1-ATPase (TF1), which have different behavior.

Adenosine Triphosphate↗