Quantum Molecular Biological Methods Using Density Functional Theory

Abstract

AbstractThe fields of quantum molecular biophysics and quantum molecular biology have recently experienced a revival. With the extension of density functional theoretical (DFT) methods to quantum chemistry, molecular biophysics and physical biology, the fundamental accuracy and physical rigor of the modeling and simulations have increased. Early modeling and simulations usedad hocmethods and semiempirical models, which were of limited accuracy and only gave qualitative results and trends. In addition, the treatment of the environment was either completely neglected or treated with distance dependent dielectrics and/or simple continuum models. With the development of first the generalized gradient approximation (GGA), then hybrid exchange correlation functionals, and finally rigorous optimized effective potentials (OEPs) for both exchange and correlation, density functional methods are now fast approaching the accuracy of the highest levels ofab initiowave function quantum mechanics methods, but at a reduced computational cost, which has allowed modeling and simulation studies to be performed on larger and more complex systems. In addition, one has recently realized that the environment is not a background for the biophysical and biochemical events, but an active participant. Hence, the inclusion of the solvent, cations, anions, and spectator species are all important and fundamental and must be included, along with the molecules and/or molecular complexes, which were formerly thought to be the fundamental entities of interest. The use of spectroscopic methods has been the key to unraveling and understanding the complexity of quantum molecular biological events and processes. But the tools to use to probe the events and processes may influence what one is trying to measure and/or observe, especially when one uses X‐ray radiation, as has been observed in many cases. Hence, the combination of both many spectroscopic methods and simulations techniques has been the answer to how to best understand and interpret the results of many supposedly contradictory experimental results. By only including part of the system in the simulations, or using limited time, space, and radiation (energy) windows, one has only taken snapshots of the complex biological processes and then tried to tell the story. This is like taking a few frames from a movie and trying to determine the complete story line, an almost impossible task. In this review, we present some of our fundamental contributions to this field, include those of other groups, and finally present what we see as the future, in terms of both modeling quantum molecular biological methods, but also of further extending the modeling and simulation methods to even more complex biological, interpersonal and even societal events and interactions. Mathematics and modeling are only tools which can be used to try to understand and quantify the world around us. But we must always remember that we are developing models, and the ultimate use and utility of our models and methods is their ability to reproduce physical reality, with the inputs being the various physical observables that we can measure and determine.