Institute for Protein Design, University of Washington, Seattle, WA, USA.
Knight Campus, University of Oregon, Eugene, OR, USA.
Methods Mol Biol. 2022;2371:63-100. doi: 10.1007/978-1-0716-1689-5_5.
Structure-based computational design methods have been developed to create proteins in silico with diverse shapes and sizes that accurately fold in vitro, from 7-residue macrocycles to megadalton-scale self-assembling nanomaterials. Precise control over protein shape has further enabled design and optimization of functional therapeutic proteins, including agonists, antagonists, enzymes, and vaccines. Computational design of functional peptides of smaller size presents a persistent challenge, with few successful examples to date. Herein we describe validated general methods for computational design of peptides using the Rosetta molecular modeling suite and discuss outstanding challenges and future directions.
基于结构的计算设计方法已经被开发出来，可以在计算机上创建具有不同形状和大小的蛋白质，这些蛋白质可以在体外精确折叠，从 7 个残基的大环到兆道尔顿规模的自组装纳米材料。对蛋白质形状的精确控制进一步使功能治疗蛋白的设计和优化成为可能，包括激动剂、拮抗剂、酶和疫苗。目前，具有更小尺寸的功能性肽的计算设计仍然是一个持续的挑战，成功的例子很少。本文中，我们描述了使用 Rosetta 分子建模套件进行肽的计算设计的经过验证的一般方法，并讨论了尚未解决的挑战和未来的方向。
