Application of Large-Scale First Principles Quantum Mechanical Calculations With the ONETEP Program To Biophysical Problems

Abstract

Properties and processes at the molecular level are determined by the interactions between electrons and atomic nuclei whose motions are governed by the theory of quantum mechanics. Therefore, an unbiased and highly accurate approach for molecular simulations can be provided by quantum mechanical calculations from “first principles”, which do not rely on empirical parameters. Density Functional Theory (DFT) is such an approach and is widely used because of its computational efficiency but the computational effort of conventional DFT increases with the third power of the number of atoms. As a result it is practically not feasible even on supercomputers to perform DFT calculations with more than a few hundred atoms. Novel reformulations of DFT based on the one-particle density matrix can lead to computational effort which increases linearly with the number of atoms and hence overcome this length-scale problem. I will briefly describe how this is achieved in our ONETEP linear-scaling DFT program which is designed to achieve the same high level of accuracy as conventional cubic-scaling approaches. Then I will give an overview of current applications we are performing with ONETEP, including quantum mechanical simulations of entire proteins with thousands of atoms participating in protein-protein and protein-ligand complexes.[1] C.-K. Skylaris, P. D. Haynes, A. A. Mostofi and M. C. Payne. J. Chem. Phys. 122 (2005) 084119.[2] L. Heady, M. Fernandez-Serra, R. L. Mancera, S. Joyce, A. R. Venkitaraman, E. Artacho, C.-K. Skylaris, L. Colombi Ciacchi and M. C. Payne. J. Med. Chem. 49 (2006) 5141.[3] C.-K. Skylaris, P. D. Haynes, A. A. Mostofi and M. C. Payne. J. Phys. Condens. Matter 20 (2008) 064209.