Integrative Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Methods Mol Biol. 2021;2262:311-321. doi: 10.1007/978-1-0716-1190-6_19.
This chapter will describe how mathematical modeling allows the RAS pathway to be studied with computational experiments. The mathematical model utilized simulates the biochemical reactions that regulate RAS signaling. This type of model incorporates knowledge of reaction mechanisms, including measured quantitative parameters that characterize these reactions for both wild-type and mutant RAS proteins. For an illustrative example, this chapter focuses on how modeling provided new insights that helped solve a problem that challenged the RAS community for nearly a decade: why do colorectal cancers with the KRAS G13D mutation, but not the other common KRAS mutations, benefit from EGFR inhibition? The methods described include computational dose-response experiments and the use of "computational chimeric" RAS mutants.
本章将介绍如何通过计算实验来研究 RAS 通路，使用的数学模型模拟了调节 RAS 信号的生化反应。该模型结合了反应机制的知识，包括用于野生型和突变型 RAS 蛋白的这些反应的测量定量参数。作为一个说明性示例，本章重点介绍了建模如何提供新的见解，帮助解决了 RAS 领域近十年来一直面临的挑战：为什么具有 KRAS G13D 突变的结直肠癌受益于 EGFR 抑制，而不是其他常见的 KRAS 突变？所描述的方法包括计算剂量反应实验和使用“计算嵌合”RAS 突变体。
