Earticle

초록

영어

Through the processes of natural selection and co-option, nature has crafted an astounding array of protein designs with a remarkable repertoire of functions ranging from catalysis to signaling and regulation. A growing list of biotechnology needs for proteins with altered cofactor/substrate specificities, improved/modified functionalities or activities are creating an ever expanding compilation of protein design challenges. Two separate tracks of computational methods will be described depending on the presence or absence of detailed structural information. The first track of methods will concentrate on the design of a known protein structure to introduce an improved or completely novel function such as affinity for a cofactor, substrate, or small molecule (ligand). This will be accomplished by either modifying the existing active site (i.e., redesign) to bring about an altered functionality or by introducing a completely new active site into the fold when a novel functionality is sought. Computations will be first tested by altering the effector binding specificity of the bacterial transcriptional regulatory protein AraC to molecules other than L-arabinose and by grafting a calcium binding pocket onto a cell adhesion protein. The second track of methods will focus on protein design challenges when detailed structural information is absent and limited information is available regarding residue contacts or function. Instead, only the sequences of protein family members are available. In such instances, protein design efforts typically rely on the high throughput screening of large combinatorial libraries generated by accumulating single point mutations and/or recombination events. Here, scoring functions will be put forth and computations will be used to identify the optimal pattern of point mutations and/or recombination events that are likely to maximize functional enrichment in a combinatorial protein library of a pre-specified size. We will benchmark the efficiency of all computational methods by comparing their performance on P450 and beta-lactamase libraries.

저자

• Costas Maranas [ Department of Chemical Engineering The Pennsylvania State University, USA ]

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  한국생물공학회 학술대회

• 간기

  반년간

• 수록기간

  1985~2013

• 십진분류

  KDC 476 DDC 576