Classical And Ab Initio Molecular Dynamics Study Of The Catalytic Core Of Kinesin

Life implies movement. Most forms of movement in the living world are powered by tiny protein machines known as molecular motors. These motors transport a wide variety of cargo along protein tracks in the cytoplasm, power cell locomotion, drive cell division. Motor defects can lead to severe diseases or may even be lethal. The motor protein kinesin moves along microtubules, driven by adenosine triphosphate (ATP) hydrolysis. Although kinesin's function has been studied extensively through experiments, it remains unclear how kinesin hydrolyzes ATP and converts the chemical energy into mechanical movement. On these issues in the study of the current life sciences, it's one of the most forefront-topics.In the past two decades, both computational chemistry and life science have been greatly developed, and their close combination resulted in a new crossed subject - computational molecular biology. Computational molecular biology has been applied extensively and successfully in lots of aspects of life science, especially in the studies of protein folding, structural prediction of proteins.Among the methods of computational molecular biology, molecular dynamics has been proved to be a powerful tool in simulating dynamic properties of proteins. Car-Parrinello molecular dynamics (CPMD), also developed in the past two decades, is an ab initio molecular dynamics'method based on density functional theory and classical molecular dynamics.In this paper, we base our research on the reported crystal structures of motor kinesin and use classical molecular dynamics and ab initio molecular dynamics to study the catalytic core of kinesin.The release of phosphate (Pi) from the catalytic core of kinesin is a crucial step in the chemo-mechanical transduction process. Thus, to understand the release route of Pi and the interaction of Pi with the kinesin's catalytic core must be characterized. We use molecular dynamics simulation to model the process of Pi release and find the close relationship between the"back door"of kinesin and the release route of Pi. While Pi release, the conformation of super-secondary structure loop11-α4-loop12 in kinesin changes remarkably. Based on these dynamic modeling informations, we speculate a mechanism to detail Pi release.Now, CPMD has become the most important molecular dynamics method based on the first principle theory. After learning efforts,we have the capability to use this technology to investigate the complex chemical and physical behavior of reactive systems. Here, we use Car-Parrinello molecular dynamics to research the catalysis mechanism in kinesin. In our study, we find that three key waters activate theγ-phosphate of ATP and these three key waters have the most possibility to catalyse ATP through their"direct attacking"or"assisted attacking"pathway.