Effects of distance constraints on macromolecular conformation. II. Simulation of experimental results and theoretical predictions
Effects of distance constraints on macromolecular conformation. II. Simulation of experimental results and theoretical predictions
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距离限制对大分子构象的影响。
DOI：
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发表时间：
1979
期刊：
影响因子：
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通讯作者：
I. Kuntz
中科院分区：
文献类型：
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作者：
Timothy F. Havel;G. Crippen;I. Kuntz
通过生成胰蛋白酶抑制剂和鲤鱼肌原的随机结构类别，每个结构都与一组给定的实验或理论信息一致，我们评估了各种实验和理论在推导大分子构象方面的相对效用。我们将计算出的结构与已知的 X 射线坐标进行比较，并计算每个类别的平均误差。小误差意味着实验或理论约束将结构限制在晶体结构附近，而大误差则表明约束允许多种三级构象。我们发现以下几点是正确的：（1）所有距离的定性信息（可能从残基间接触的正确预测中获得）有效地确定了结构（误差约为 1 Å）。 (2) 仅当给定的距离数量与残基数量相当时（可能从核磁共振或交联实验中获得），有限数量的距离的定量信息才会显着限制可能结构的范围（误差约为 3 Å）。 (3) 关于每个残基到分子质心的距离的定量信息，可能部分来自溶剂可及性和溶液 X 射线研究，其本身并没有特别的限制（误差约为 5 Å）。 (4) 完整的定性局部距离信息（可能从二次预测和 CD/ORD 研究中获得）显然与各种三级结构一致（误差约为 7 Å）。
By generating classes of random structures for trypsin inhibitor and carp myogen, each consistent with a given set of experimental or theoretical information, we have assessed the relative utility of various experiments and theories in deducing the conformation of macromolecules. We compare the calculated structures with known x‐ray coordinates and compute for each class an average error. Small errors mean that the experimental or theoretical constraints limit the structures to the vicinity of the crystal structure, whereas large errors show that the constraints permit a wide variety of tertiary conformations. We find the following points to hold true: (1) Qualitative information on all the distances, as might be obtained from the correct prediction of interresidue contacts, effectively determines the structure (error approximately 1 Å). (2) Quantitative information on a limited number of distances, as might be obtained from nmr or crosslinking experiments, significantly restricts the range of possible structures only when the number of distances given is comparable to the number of residues (error approximately 3 Å). (3) Quantitative information on the distances of each residue to the center of mass of the molecule, as might in part be obtained from solvent accessibility and solution x‐ray studies, is not particularly restrictive by itself (error approximately 5 Å). (4) Complete qualitative local distance information, as might be obtained from secondary prediction and CD/ORD studies, is clearly consistent with a wide variety of tertiary structures (error approximately 7 Å).