Motor proteins are active enzymatic molecules that are critically important for a variety of biological phenomena. It is known that some neurodegenerative diseases are caused by specific mutations in motor proteins that lead to their malfunctioning. Hereditary spastic paraplegia is one of such diseases, and it is associated with the mutations in the neuronal conventional kinesin gene, producing the decreased speed and processivity of this motor protein. Despite the importance of this problem, there is no clear understanding on the role of mutations in modifying dynamic properties of motor proteins. In this work, we investigate theoretically the molecular basis for negative effects of two specific mutations, N2565 and R280S, on the dynamics of kinesin motor proteins. We hypothesize that these mutations might accelerate the adenosine triphosphate (ATP) release by increasing the probability of open conformations for the ATP-binding pocket. Our approach is based on the use of coarse-grained structure-based molecular dynamics simulations to analyze the conformational changes and chemical transitions in the kinesin molecule, which is also supplemented by investigation of a mesoscopic discrete-state stochastic model. Computer simulations suggest that mutations N256S and R280S can decrease the free energy difference between open and closed biochemical states, making the open conformation more stable and the ATP release faster, which is in agreement with our hypothesis. Furthermore, we show that in the case of N256S mutation, this effect is caused by disruption of interactions between a helix and switch I and loop Ll 1 structural elements. Our computational results are qualitatively supported by the explicit analysis of the discrete-state stochastic model.