期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 19, 页码 7304-7309出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1112595109
关键词
biomaterials; computational protein design; crystal engineering; protein crystallization; self-assembly
资金
- Penn Nano/Bio Interface Center (National Science Foundation NSEC) [DMR-0425780]
- US Department of Energy [DE-FG02-04ER46156]
- National Institutes of Health [HL085303, GM54616]
- Direct For Mathematical & Physical Scien
- Division Of Materials Research [1120901] Funding Source: National Science Foundation
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [0832802] Funding Source: National Science Foundation
Protein crystals have catalytic and materials applications and are central to efforts in structural biology and therapeutic development. Designing predetermined crystal structures can be subtle given the complexity of proteins and the noncovalent interactions that govern crystallization. De novo protein design provides an approach to engineer highly complex nanoscale molecular structures, and often the positions of atoms can be programmed with sub-angstrom precision. Herein, a computational approach is presented for the design of proteins that self-assemble in three dimensions to yield macroscopic crystals. A three-helix coiled-coil protein is designed de novo to form a polar, layered, three-dimensional crystal having the P6 space group, which has a honeycomb-like structure and hexameric channels that span the crystal. The approach involves: (i) creating an ensemble of crystalline structures consistent with the targeted symmetry; (ii) characterizing this ensemble to identify designable structures from minima in the sequence-structure energy landscape and designing sequences for these structures; (iii) experimentally characterizing candidate proteins. A 2.1 angstrom resolution X-ray crystal structure of one such designed protein exhibits sub-angstrom agreement [backbone root mean square deviation (rmsd)] with the computational model of the crystal. This approach to crystal design has potential applications to the de novo design of nanostructured materials and to the modification of natural proteins to facilitate X-ray crystallographic analysis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据