Work

Computationally Assisted Noncanonical Amino Acid Incorporation

Year: 2024

Type: article

Abstract: Genetic encoding of noncanonical amino acids (ncAAs) with desired functionalities is an invaluable tool for the study of biological processes and the development of therapeutic drugs. However, existing ncAA incorporation strategies are rather time-consuming and have relatively low success rates. Here, we develop a virtual ncAA screener based on the analysis and modeling of the chemical properties of all reported ncAA substrates to virtually determine the recognition potential of candidate ncAAs. Using this virtual screener, we designed and incorporated several novel Lys and Phe derivatives into proteins for various downstream applications. Among them, the genetic encoding of an electron-rich Phe analog, 3-dimethylamino-phenylalanine, was successfully applied to enhance the cation-π interaction between histone methylation and its reader proteins. Thus, our virtual screener provides a fast and powerful strategy to efficiently incorporate ncAAs with diverse functionalities.

Source: ACS Central Science

DOI: 10.1021/acscentsci.4c01544

Authors: Chengzhu Fang, Wenyuan Xu, Chao Liu, Yulin Chen, Shixian Lin, Wenlong Ding

Institutions: Second Affiliated Hospital of Zhejiang University, Zhejiang University

Language: English

Topic: RNA and protein synthesis mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: diamond

Funders: National Natural Science Foundation of China, Zhejiang University, National Key Research and Development Program of China, Natural Science Foundation of Zhejiang Province