Atomistic simulations have been widely used to study deformation mechanisms of plasticity in metals and alloys. While being very effective for illuminating the controlling mechanisms in detail, direct atomistic simulations have many limitations such as short timescales and small spatial scales, when used to study large systems. Those limitations emerge when one desires to study materials under conditions more typical of application. My research is aimed to address the short-timescales challenges in atomistic simulations with relevant indirect approaches. I explore dislocation problems in different systems using several approaches and figure out relevant approaches for the chosen problems by comparing their performance. First, I adapt MD to simulate dislocation nucleation in a small 2D fcc Al simulation box with a cylindrical nanovoid inside. This problem serves as a test problem to validate indirect approaches conducted. I show that a variational TST approach, with the support of the finite temperature string (FTS) method, predicts dislocation nucleation rates in accordance with direct MD simulations. The work provides energetics information to illuminate the free energy characteristics of the system that explain the errors of approaches to predicting nucleation expectation time. Second, I build bigger simulation cells to study problems of dislocation nucleation from a faceted surface and from spherical nanovoids of different sizes. The problems are studied at realistic timescales in a variational TST framework, exploiting the FTS meth- ods. Dislocation nucleation from surface study can be related to the strength of sub-micron Al wires. From the results, I make predictions for maximum attainable strength of Al nanowires, and for the associated strain rate sensitivity. The study of dislocation nucleation from voids is relevant to studying void growth mechanisms. My results contribute to a long-standing debate regarding what are the controlling mechanisms in void growth. Third, I study the interaction between dislocation and nanometer-size coherent metastable precipitates. These precipitates serve as impeders to dislocation mobility and hence help enhance alloy strength. I show here that transition in such systems is so complex that a typical transition tube in FTS cannot be practically defined. However, we can use part of the information from FTS computation to employ another sampling method, the transition interface sampling (TIS), for obtaining reaction rates of events in the systems with errors within an order of magnitude.