and [32]. The fact that the rational protein design methods through computational models have been developed and it have provided a new valuable tool for improving enzyme properties to the desired requirements [33]. This method has experienced important with varying degrees of success in recent years, with considerable achievements in the design of novel enzymes [34], [35] and [36]. Structural features of an enzyme can affect the thermostability as well as plays a crucial role in promoting thermostability. For example, thermostability is associated with large numbers of electrostatic interactions, a large number and tight metal-binding sites, high packing density and core hydrophobicity. Thus, a rational approach (e.g. site-directed mutagenesis) can be used in the presence of empirical testing to enzyme engineering as well as optimizing the activity and thermal properties of an enzyme [37]. Understanding the structural basis of altered properties of proteins due to changes, provides useful insight in designing proteins with improved catalytic activity or thermostability. We describe here progress in improving the stability and activity of SML by rational site-directed mutagenesis (SDM) based on homology modeling and molecular dynamics (MD) simulations as well as experimentally testing. In this study, four mutant proteins of SML were designed and constructed, and was analyzed enzyme activity and thermostability.