Excited state dynamics in the early stages of the bR and Rh photocycle

在这个提议中考虑的所有视网膜蛋白质的复杂功能的第一步是光的吸收，随后是蛋白质内发色团的异构化。该方法的高速度、效率和选择性与结合口袋的优化分子排列直接相关。到目前为止，不同的因素限制了这些系统的理论描述。首先，反应发生在激发电子态，量子化学计算只能以高计算成本提供精确的解决方案。其次，视网膜蛋白质的动力学被认为发生在强耦合的势能表面上。这使得使用先进的非绝热分子动力学计划的强制性，以获得现实的反应时间尺度和量子产率的值。最后，蛋白质与发色团相互作用的复杂性要求在活性位点的结构模型中包含大部分结合口袋，这涉及高计算量。因此，在本项目中，我们将使用最近开发的近似但预测的方法来分析bR和Rh光循环的早期阶段。在对用于验证该方法的小视网膜模型进行初步计算后，我们将对蛋白质的结构模型进行非绝热分子动力学模拟，并增加其复杂性。也就是说，我们逐步完善的模型，包括越来越多的相邻官能团和氨基酸的发色团周围。通过这种方式，我们希望确定重要的相互作用，使bR和Rh蛋白质达到其接近最佳的效率。最后，设想使用TDQM-MM方法模拟整个蛋白质。这些计算将提供光循环中间体的结构信息，并导致复杂的视网膜光反应的详细图片。

The very first step in the complex function of all the retinal proteins considered in this proposal is the absorption of light which is followed by an isomerization of the chromophore within the protein. The high speed, efficiency and selectivity of the process are directly related to the optimized molecular arrangement of the binding pocket. Different factors have so far limited the theoretical description of these systems. First, the reaction occurs in an excited electronic state for which quantum chemical calculations provide accurate solutions only at high computational cost. Second, the dynamics in the retinal proteins are believed to happen on strongly coupled potential energy surfaces. This makes the use of advanced nonadiabatic molecular dynamics schemes mandatory in order to obtain realistic values for reaction time scales and quantum yields. Finally, the complexity of the protein interaction with the chromophore requires the inclusion of a large part of the binding pocket in structural models for the active site, which involves a high computational effort. In this project we will therefore use a recently developed approximate but yet predictive method to analyze the early stages of the bR and Rh photocycles. After preliminary calculations on small retinal models used to validate the method, we will perform nonadiabatic molecular dynamic simulations on structural models of the protein with increasing complexity. That is, we stepwise refine the model by inclusion of more and more neighbouring functional groups and amino acids in the chromophore surrounding. In this way we hope to identify the important interactions which allow the bR and Rh proteins to achieve their near optimal efficiency. Finally, simulations of the whole protein are envisaged using a TDQM-MM approach. These calculations will provide structural information on intermediates in the photocycle and lead to a detailed picture of the complex retinal photoreaction.