IMPROVEMENTS IN THE NUMERICAL-ANALYSIS OF THERMODYNAMIC DATA FROM BIOMOLECULAR COMPLEXES
IMPROVEMENTS IN THE NUMERICAL-ANALYSIS OF THERMODYNAMIC DATA FROM BIOMOLECULAR COMPLEXES
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DOI：
10.1006/abio.1993.1155
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发表时间：
1993-04-01
影响因子：
2.9
通讯作者：
ROYER, CA
中科院分区：
文献类型：
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作者：
ROYER, CA
在这项工作中，最近的改进能力的数值求解器为基础的绑定数据的全球分析程序，BIOEQS，提出。这些改进代表了可以考虑的物理模型类型的扩展。改进的第一个领域涉及的系统，其中包括几个物种的相同的化学计量和不同的化学势，或网站异构体的建模。这种选择通常用于分析多个配体与多个蛋白质位点的结合。除了经典的配体结合问题之外，这种能力在考虑蛋白质与同一DNA分子上的不同位点的结合以及连接对这些平衡的影响时是有用的。它也可以用于考虑与折叠的单体中间体的寡聚蛋白质的平衡解折叠。稀释的蛋白质和连接多达两种不同类型的配体在多个结合位点后的解离和解折叠的低聚物的性质的影响，现在是可能的。第二个进步已被纳入BIOEQS程序的建模能力是考虑扰动的化学变性剂，温度，或高静水压力的多重结合或折叠平衡的选项。BIOEQS程序的其他改进包括将单个物种或物种总和直接映射到数值物理实验观测值。对应于特定物质或0和100%滴定完成的可观察值可以是拟合中的固定或浮动参数。这些变化结合在一起，大大拓宽了程序的应用，允许模拟几乎任何组合的物种之间的相互作用，三种类型的生物分子，探索沿着几乎任何热力学实验轴，并映射到几乎任何实验观察。
In this work, recent improvements in the capability of the numerical solver-based binding data global analysis program, BIOEQS, are presented. These improvements represent an expansion of the types of physical models which can be considered. The first realm of improvement concerns the modeling of systems which include several species of the same stoichiometry and differing chemical potentials, or site isomers. Such an option is generally used in the analysis of binding of multiple ligands to multiple protein sites. In addition to classical ligand binding problems, such a capability is useful in considering the binding of protein to different sites on the same DNA molecule and the effects of ligation upon these equilibria. It can also be employed for consideration of the equilibrium unfolding of oligomeric proteins with folded monomeric intermediates. The effect of dilution of the protein and ligation by up to two different types of ligands at multiple binding sites upon the dissociation and unfolding properties of the oligomers is now possible. The second advance which has been incorporated into the modeling capabilities of the BIOEQS program is the option of considering perturbations to the multiple binding or folding equilibria by chemical denaturants, temperature, or high hydrostatic pressure. Additional improvements to the BIOEQS program include direct mapping of individual species or sums of species to the numerical physical experimental observable. The values of the observable corresponding to particular species or to 0 and 100% completion of a titration can be either fixed or floating parameters in the fit. These changes taken together considerably broaden the applications of the program, allowing modeling of virtually any combination of species resulting from the interactions between three types of biomolecules, exploration along virtually any thermodynamic experimental axis, and mapping to virtually any experimental observable.