The tertiary structure of a native protein is dictated by the interplay of local secondary structure propensities, hydrogen bonding, and tertiary interactions. It is argued that the space of known protein topologies covers all single domain folds and results from the compactness of the native structure and excluded volume. Protein compactness combined with the chirality of the protein's side chains also yields native-like Ramachandran plots. It is the many-body, tertiary interactions among residues that collectively select for the global structure that a particular protein sequence adopts. This explains why the recent advances in deep-learning approaches that predict protein side-chain contacts, the distance matrix between residues, and sequence alignments are successful. They succeed because they implicitly learned the many-body interactions among protein residues.

天然蛋白质的三级结构由局部二级结构倾向、氢键和三级相互作用的相互作用决定。有人认为，已知蛋白质拓扑的空间覆盖了所有单域折叠，并且是由于天然结构的紧凑性和排除体积的结果。蛋白质紧密性与蛋白质侧链的手性相结合，也产生了类似天然的 Ramachandran 图。正是残基之间的多体、三级相互作用共同选择了特定蛋白质序列采用的全局结构。这解释了为什么预测蛋白质侧链接触、残基之间的距离矩阵和序列比对的深度学习方法的最新进展是成功的。