Adaptive Accelerated Molecular Dynamics (Ad-AMD) Revealing the Molecular Plasticity of P450cam.
Adaptive Accelerated Molecular Dynamics (Ad-AMD) Revealing the Molecular Plasticity of P450cam.
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DOI：
10.1021/jz101462n
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发表时间：
2011-02-03
期刊：
影响因子：
--
通讯作者：
McCammon JA
中科院分区：
文献类型：
--
作者：
Markwick PR;Pierce LC;Goodin DB;McCammon JA
提出了一种扩展的加速分子动力学（AMD）方法，称为自适应AMD。自适应AMD（Ad-AMD）是一种高效、鲁棒的构象空间采样算法，特别适用于具有高度结构化势能表面的蛋白质，这些势能表面表现出复杂、大规模的集体构象转变。无底物P450 cam的Ad-AMD模拟表明，该系统存在于完全和部分开放构象状态之间的平衡。底物结合的机制取决于配体的大小。较大的配体进入P450 cam结合口袋，并且所得到的底物结合系统通过群体转移机制被捕获在开放构象中。完全进入结合口袋的小配体引起诱导配合机制，导致形成能量稳定的闭合构象状态。最近的实验研究证实了这些结果，并可能提供详细的了解整个细胞色素P450超家族的功能动力学和构象行为。
An extended accelerated molecular dynamics (AMD) methodology called adaptive AMD is presented. Adaptive AMD (Ad-AMD) is an efficient and robust conformational space sampling algorithm that is particularly-well suited to proteins with highly structured potential energy surfaces exhibiting complex, large-scale collective conformational transitions. Ad-AMD simulations of substrate-free P450cam reveal that this system exists in equilibrium between a fully and partially open conformational state. The mechanism for substrate binding depends on the size of the ligand. Larger ligands enter the P450cam binding pocket, and the resulting substrate-bound system is trapped in an open conformation via a population shift mechanism. Small ligands, which fully enter the binding pocket, cause an induced-fit mechanism, resulting in the formation of an energetically stable closed conformational state. These results are corroborated by recent experimental studies and potentially provide detailed insight into the functional dynamics and conformational behavior of the entire cytochrome-P450 superfamily.
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影响因子：
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作者：
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