%0 Journal Article %T Computational protein design approaches with significant biological outcomes: progress and challenges %A Xiaoman Li %A Ziding Zhang %A Jiangning Song %J Computational and Structural Biotechnology Journal %D 2012 %I Research Network of Computational and Structural Biotechnology %X Enzymes are powerful biocatalysts, however, so far there is still a large gap between the number of enzyme-based practical applications and that of naturally occurring enzymes. Multiple experimental approaches have been applied to generate nearly all possible mutations of target enzymes, allowing the identification of desirable variants with improved properties to meet the practical needs. Meanwhile, an increasing number of computational methods have been developed to assist in the modification of enzymes during the past few decades. With the development of bioinformatic algorithms, computational approaches are now able to provide more precise guidance for enzyme engineering and make it more efficient and less laborious. In this review, we summarize the recent advances of method development with significant biological outcomes to provide important insights into successful computational protein designs. We also discuss the limitations and challenges of existing methods and the future directions that should improve them. %U http://journals.sfu.ca/rncsb/index.php/csbj/article/view/csbj.201209007