This is a tour of a physical chemist through 65 years of protein chemistry from the time when emphasis was placed on the determination of the size and shape of the protein molecule as a colloidal particle, with an early breakthrough by James Sumner, followed by Linus Pauling and Fred Sanger, that a protein was a real molecule, albeit a macromolecule. It deals with the recognition of the nature and importance of hydrogen bonds and hydrophobic interactions in determining the structure, properties, and biological function of proteins until the present acquisition of an understanding of the structure, thermodynamics, and folding pathways from a linear array of amino acids to a biological entity. Along the way, with a combination of experiment and theoretical interpretation, a mechanism was elucidated for the thrombin-induced conversion of fibrinogen to a fibrin blood clot and for the oxidative-folding pathways of ribonuclease A. Before the atomic structure of a protein molecule was determined by x-ray diffraction or nuclear magnetic resonance spectroscopy, experimental studies of the fundamental interactions underlying protein structure led to several distance constraints which motivated the theoretical approach to determine protein structure, and culminated in the Empirical Conformational Energy Program for Peptides (ECEPP), an all-atom force field, with which the structures of fibrous collagen-like proteins and the 46-residue globular staphylococcal protein A were determined. To undertake the study of larger globular proteins, a physics-based coarse-grained UNited-RESidue (UNRES) force field was developed, and applied to the protein-folding problem in terms of structure, thermodynamics, dynamics, and folding pathways. Initially, single-chain and, ultimately, multiple-chain proteins were examined, and the methodology was extended to protein–protein interactions and to nucleic acids and to protein–nucleic acid interactions. The ultimate results led to an understanding of a variety of biological processes underlying natural and disease phenomena.

中文翻译：

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我从事蛋白质化学 65 年

这是一位物理化学家的 65 年蛋白质化学之旅，从重点放在确定作为胶体颗粒的蛋白质分子的大小和形状开始，詹姆斯·萨姆纳 (James Sumner) 和莱纳斯·鲍林 (Linus Pauling) 取得了早期突破和弗雷德桑格，蛋白质是一个真正的分子，尽管是一个大分子。它涉及对氢键和疏水相互作用在确定蛋白质的结构、性质和生物学功能方面的性质和重要性的认识，直到目前从氨基线性阵列中获得对结构、热力学和折叠途径的理解。酸对生物实体。一路走来，结合实验与理论解读，阐明了凝血酶诱导的纤维蛋白原转化为纤维蛋白血凝块和核糖核酸酶 A 的氧化折叠途径的机制。在通过 X 射线衍射或核磁共振光谱确定蛋白质分子的原子结构之前，实验对蛋白质结构基础相互作用的研究导致了几个距离限制，这些限制激发了确定蛋白质结构的理论方法，并最终导致了肽经验构象能量计划 (ECEPP)，这是一种全原子力场，纤维的结构测定了胶原蛋白样蛋白和 46 个残基的球状葡萄球菌蛋白 A。为了研究较大的球状蛋白质，开发了一种基于物理的粗粒度联合残差 (UNRES) 力场，并在结构、热力学、动力学和折叠途径方面应用于蛋白质折叠问题。最初，检查单链和最终的多链蛋白质，并将该方法扩展到蛋白质-蛋白质相互作用、核酸和蛋白质-核酸相互作用。最终结果使人们了解了自然和疾病现象背后的各种生物过程。