Quantum Chemical Evaluation of Inter- and Intra-molecular Interactions in Proteins

该项目的总体目标是利用现代量子化学，对生物分子系统中的分子间和分子内相互作用提供准确和独特的见解，使用溶剂的连续表示。线性尺度半经验分而治之算法加上标准的泊松-玻尔兹曼理论将被应用到生物学相关的问题，研究蛋白质分子间和分子内的相互作用。经典的MD模拟和单点QM计算将进行估计的蛋白质的介电常数的值。泊松-玻尔兹曼电荷转移方法的电荷转移效应的纳入将进一步发展。卷曲螺旋和盐桥蛋白质和肽的相互作用产生的实验信息将被用来验证的方法。 由于计算机硬件和薛定谔方程数值算法的进步，量子化学现在可以在全原子水平上为我们理解大分子结构和功能做出贡献。 现代量子化学方法提供了几个基于经典方法的优点：（1）静电表示更准确，因为环境，构象，极化和电荷转移效应明确包括不同于经典模型。(2)没有必要定义介电常数，因为介电弛豫明确包括在QM模型中。(3)量子化学方法可以改进的方式已经被彻底记录（即，在基组中纳入相关性和改进）。该项目将对可应用于重要生物学问题的新型量子力学方法的发展产生广泛影响。 该研究项目将培养学生的正式理论，计算机编程，生物结构和手稿准备/出版。学生也将有机会与其他生物组在宾夕法尼亚州立大学和其他大学在美国和国外互动。事实上，每个学生将被要求每年至少参加一次国家或国际会议，以海报或口头形式展示他/她的成果。 已经建立了一个量子生物信息学数据库（QDB：http：//qbiodb.chem.psu.edu/），这将有助于传播和分析这项工作的结果。 这项工作由化学部的理论和计算化学计划以及分子和细胞生物科学部的分子生物物理计划共同资助。

The overall goal of this project is to use modern quantum chemistry to provide accurate and unique insights into inter and intramolecular interactions in biomolecular systems, using a continuum representation for the solvent. The linear-scaling semi empirical divide and conquer algorithm coupled with standard Poisson-Boltzmann theory will be applied to biologically relevant problems to study inter and intramolecular interactions in proteins. Classical MD simulations and single point QM calculations will be carried out to estimate the value of the dielectric constant of a protein. The Poisson-Boltzmann charge transfer approach for the incorporation of charge transfer effects will be further developed. Experimental information generated on coiled-coil and salt bridge interactions in proteins and peptides will be used to validate the approach. Given the advances in computer hardware and in numerical algorithms for the solution of the Schrodinger equation, quantum chemistry can now realistically contribute at the all-atom level to our understanding of macromolecular structure and function. Modern quantum chemical approaches offer several advantages over classically based methods: (1)The electrostatic representation is more accurate because environmental, conformational, polarization and charge transfer effects are explicitly included unlike classical models. (2) There is no need to define the dielectric constant because dielectric relaxation is explicitly included in QM models. (3) The ways in which quantum chemical methods can be improved have been thoroughly documented (i.e., inclusion of correlation and improvements in the basis set). This project will have a broad impact on the development of novel quantum mechanical approaches that can be applied to important biological problems. The research project will train students in formal theory, computer programming, biological structure and manuscript preparation/publication. The students will also have the opportunity to interact with other biological group at Penn State and at other universities in the USA and abroad. Indeed, each student will be required to attend at least one national or international meeting per year to present his/her results in either a poster or oral format. A quantum bioinformatics database (QDB: http://qbiodb.chem.psu.edu/) has been created, which will aid in the dissemination and analysis of results from this work. This work is funded jointly by the Theoretical and Computational Chemistry Program in the Chemistry Division and the Molecular Biophysics Program in the Division of Molecular and Cellular Biosciences.