ESTIMATION OF EFFECTIVE INTERRESIDUE CONTACT ENERGIES FROM PROTEIN CRYSTAL-STRUCTURES - QUASI-CHEMICAL APPROXIMATION
ESTIMATION OF EFFECTIVE INTERRESIDUE CONTACT ENERGIES FROM PROTEIN CRYSTAL-STRUCTURES - QUASI-CHEMICAL APPROXIMATION
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DOI：
10.1021/ma00145a039
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发表时间：
1985-01-01
期刊：
影响因子：
5.5
通讯作者：
JERNIGAN, RL
中科院分区：
文献类型：
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作者：
MIYAZAWA, S;JERNIGAN, RL
蛋白质在溶液中的有效interresidue接触能估计从观察到的球状蛋白质的晶体结构中的残基-残基接触的数量通过准化学近似与近似处理的链连接性的影响。采用格点模型，蛋白质的每个残基被假定为占据格点中的一个位点，而空位被认为是被有效溶剂分子占据，该有效溶剂分子的大小等于残基的平均大小。一个基本的假设是，在大量的蛋白质晶体结构中形成的残基-残基接触的平均特征反映了残基之间相互作用的实际差异，好像每个蛋白质中的特定氨基酸序列以及残基内和短程相互作用没有显著贡献。然后，考虑到链的连接性对体系大小的影响，即对体系中的格点数目或有效溶剂分子数目的限制，将体系看作是不连接残基和有效溶剂分子的混合物。准化学近似，即接触对的形成类似于一个化学反应，被施加到这个系统，以获得公式，涉及的接触的接触能量的数量的统计平均值。每种蛋白质的有效溶剂分子的数量被选择产生的残基-残基接触的总数等于其预期值的硬球之间的相互作用的残基和有效溶剂分子的假设情况下，在这种条件下的残基-残基接触的预期数量已粗略估计的自由连接的链分布和扩展起源于硬球相互作用。每个残基由其侧链原子位置的中心表示，残基和有效溶剂分子之间的接触被定义为6.5 μ m内的那些对，该距离是根据观察到的残基径向分布选择的;在计数接触时明确排除了沿链的最近邻对沿着。对于每种类型的残留物以及溶剂分子，从每种类型的残留物的平均体积估计配位数，并用于从残留物-残留物接触的数量评估残留物-溶剂和溶剂-溶剂接触的数量。接触能的估计值有合理的残留物类型的依赖性，反映残留物在蛋白质晶体中的分布;非极性残留物和极性残留物，以及这些残留物组的隔离。此外，Nozaki和Tanford报道的非极性残基的平均接触能与其疏水性之间存在线性关系;然而，平均值约为两倍。相关的结果蛋白质折叠和其他应用进行了讨论。
Effective interresidue contact energies for proteins in solution are estimated from the numbers of residue-residue contacts observed in crystal structures of globular proteins by means of the quasi-chemical approximation with an approximate treatment of the effects of chain connectivity. Employing a lattice model, each residueof a protein is assumed to occupy a site in a lattice and vacant sites are regarded to be occupied by an effective solvent molecule whose size is equal to the average size of a residue. A basic assumption is that the average characteristics of residue-residuecontacts formed in a large numberof protein crystal structures reflect actual differences of interactions among residues, as if there were no significant contribution from the specific amino acid sequence in each protein as well as intraresidue and short-range interactions. Then, taking account of theeffects of the chain connectivity only as imposing a limit to the size of the system, ie, the number of lattice sites or the number of effective solvent molecules in the system, the system is regarded to be the mixture ofunconnected residues and effective solvent molecules. The quasi-chemical approximation, that contact pair formation resembles a chemical reaction, is applied to this system to obtain formulas that relate the statistical averages of the numbers of contacts to the contact energies. The number of effective solvent molecules for each protein is chosen to yield the total number of residue-residue contacts equalto its expected value for the hypothetical case of hard sphere interactions among residues and effective solvent molecules; the expected number of residue-residue contacts at this condition has been crudely estimated by means of a freely jointed chain distribution and an expansion originating in hard sphere interactions. Each residue is represented by the center of its side chain atom positions, and contacts among residues and effective solvent molecules are defined to be those pairs within 6.5 Á, a distance that has been chosen on the basis of the observed radial distribution of residues; nearest-neighbor pairs along a chain are explicitly excluded in counting contacts. Coordination numbers, for each type of residue as well as for solvent molecules, are estimated from the mean volume of each type of residue and used to evaluatethe numbers of residue-solvent and solvent-solvent contacts from the numbers of residue-residue contacts. The estimated values of contact energies have reasonable residue-type dependences, reflecting residue distributions in protein crystals; nonpolar-residue-in and polar-residue-out are seen as well as the segregation of those residue groups. In addition, there is a linear relationship between the average contact energies for nonpolar residues and their hydrophobicities reported by Nozaki and Tanford; however, the magnitudes on average are about twice as large. The relevance of results to protein folding and other applications are discussed.