Department of Bioinformatics, School of Earth, Biological and Environmental Sciences, Central University of South Bihar, Gaya, Bihar 824236, India.
Department of Bioinformatics, School of Earth, Biological and Environmental Sciences, Central University of South Bihar, Gaya, Bihar 824236, India.
Biochim Biophys Acta Gen Subj. 2023 Dec;1867(12):130493. doi: 10.1016/j.bbagen.2023.130493. Epub 2023 Oct 20.
Ramachandran (ϕ, ψ) steric map was introduced in 1963 to describe available conformation space for protein structures. Subsequently, residues were observed in high-energy disallowed regions of the map. To unequivocally identify the locations of disallowed conformations of residues, we got 36 noise-free protein structures (resolution ≤1 Å, R/R ≤ 0.10). These stringent criteria were applied to rule out data or model errors or any crystallographic disorders. No disallowed conformation was found in the dataset. Further, we also examined disallowed conformations in a larger dataset (resolution ≤1.5 Å, devoid of any model errors, or disorders). The observed locations of disallowed residues are referred as disallowed spots. These spots include short loops of 3-5 residues, and locations where residues participate in disulfide bonding or intramolecular interactions or inter-molecular interactions with neighboring water, metals or ligands. Conformational sampling revealed that short loops in between secondary structures hardly have any opportunity to relieve from conformational strain. Residues involved in interactions, which provide energetic compensation for high-energy conformational states, were relieved from strain once the causative interaction was removed. The present study aims to identify disallowed spots in the native state of proteins, wherein residues are forced to be trapped in high-energy disallowed conformations. Moreover, it was also observed that pre-Pro, Ser, Asp, trans-Pro, Val, Asn & Gly have higher tendency to occur in disallowed conformation, which could be attributed to factors such as conformational restrictions, residue propensity of secondary structures and compensating sidechain and mainchain interactions, stabilizing turn-mimics.
拉马钱德兰（ϕ，ψ）立体图于 1963 年被引入，用于描述蛋白质结构的可用构象空间。随后，在该图谱的高能禁区观察到了残基。为了明确识别残基的禁阻构象的位置，我们获得了 36 个无噪声的蛋白质结构（分辨率≤1Å，R/R≤0.10）。这些严格的标准被用来排除数据或模型错误或任何晶体紊乱。在数据集内未发现禁阻构象。此外，我们还在一个更大的数据集（分辨率≤1.5Å，无任何模型错误或紊乱）中检查了禁阻构象。观察到的禁阻残基的位置被称为禁阻点。这些点包括 3-5 个残基的短环，以及残基参与二硫键或分子内相互作用或与相邻水、金属或配体的分子间相互作用的位置。构象采样表明，二级结构之间的短环几乎没有任何机会从构象应变中释放出来。一旦引起应变的相互作用被消除，参与提供高能构象状态能量补偿的相互作用的残基就会从应变中释放出来。本研究旨在识别蛋白质天然状态下的禁阻点，其中残基被迫处于高能禁阻构象。此外，还观察到前脯氨酸、丝氨酸、天冬氨酸、反脯氨酸、缬氨酸、天冬酰胺和甘氨酸更容易出现禁阻构象，这可能归因于构象限制、二级结构残基倾向和补偿侧链和主链相互作用、稳定的环模拟等因素。
