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

Pennsylvania State Univ University Park, University Park PA

Investigators

Abstract

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.