Development of Quantum Chemical Methods towards Rationalization and Optimal Design of Photoactive Proteins

The PhD thesis entitled "<em>Development of Quantum Chemical Methods towards Rationalization and Optimal Design of Photoactive Proteins</em>" by Jógvan Magnus Haugaard Olsen was handed in on October 1st 2012 and defended on October 29th 2012 at the University of Southern Denmark. The PhD degree was obtained on November 8th 2012. The evaluation committee consisted of: Assoc. Prof. Hans Jørgen Aagard Jensen, Dept. of Physics, Chemistry and Pharmacy, University of Southern Denmark, Denmark Prof. Benedetta Mennucci, Dept. of Chemistry, Univeristy of Pisa, Italy Assoc. Prof. Stephan P. A. Sauer, Dept. of Chemistry, University of Copenhagen, Denmark Abstract: In this thesis we present new developments in the pursuit of computationally efficient methods that can be used rationalize the processes that occur in photoactive proteins. We formulate an advanced polarizable embedding model rooted in so-called multilevel methods that takes advantage of the fact that the photonic processes that occur in photoactive proteins can often be localized in well-defined regions of the protein. In this model we employ the expensive but accurate quantum chemical methods only on the parts of the system that partake directly in the electronic process. The effects of the environment are incorporated by adding them to the quantum mechanical equations in an effective manner. We outline the theoretical basis of the model as well as the equations that need to be incorporated in the quantum chemical methods. The work presented here is an advancement of conventional multilevel methods in that we introduce an additional layer around the important part of the system where the interactions are described at a higher level of theory thereby allowing more accurate calculations to be performed. Furthermore, we describe some of essential elements of the implementation of the model which is an important part of the development of computationally efficient methods. Finally, we also demonstrate the model by performing numerical calculations on large molecular systems such as solute-solvent systems and photoactive proteins.

约根·马格努斯·豪高·奥尔森（Jógvan Magnus Haugaard Olsen）的博士学位论文《面向光活性蛋白质（Photoactive Proteins）合理化与优化设计的量子化学方法（Quantum Chemical Methods）开发》于2012年10月1日提交，并于2012年10月29日在南丹麦大学进行答辩。该生于2012年11月8日获得博士学位。答辩委员会成员如下：丹麦南丹麦大学物理、化学与药学院副教授汉斯·约根·阿加德·延森（Hans Jørgen Aagard Jensen）；意大利比萨大学化学系教授贝内代塔·门努奇（Benedetta Mennucci）；丹麦哥本哈根大学化学系副教授斯蒂芬·P·A·绍尔（Stephan P. A. Sauer）。

摘要：本论文围绕可用于合理化光活性蛋白质内发生过程的计算高效方法展开研究，提出了若干新进展。我们构建了基于所谓多级方法（multilevel methods）的先进可极化嵌入模型（polarizable embedding model），该模型利用了光活性蛋白质内的光过程通常可定域于蛋白质中明确区域这一特性。在该模型中，我们仅对直接参与电子过程的系统部分使用计算成本高昂但精度优异的量子化学方法（quantum chemical methods），环境的影响则以有效方式嵌入量子力学（quantum mechanical）方程中予以考虑。我们阐述了该模型的理论基础，以及需整合至量子化学方法中的相关方程。本研究相较于传统多级方法的改进之处在于，我们在系统关键区域周围引入了额外的层级，其中相互作用以更高理论水平进行描述，从而可实现更精准的计算。此外，我们还介绍了该模型实现过程中的若干核心要素，这亦是计算高效方法开发的重要环节。最后，我们通过对溶质-溶剂体系、光活性蛋白质等大型分子体系开展数值计算，对所提出的模型进行了验证。