In the FD approach we employ here, one defines an active region associated with the active site, and the cost of a geometry optimization is then essentially given by the cost associated with the active region. Д®FMO is based on dividing a large molecular system into fragments and performing ab initio calculations of fragments and their pairs, and combining their energies in the energy of the whole system (see more below). For FMO, there is also the partial energy gradient method. In this work we extend the effective fragment molecular orbital (EFMO) method, into the frozen domain (FD) formalism, originally developed for the fragment molecular orbital (FMO) method вЂ“.

Although many force fields are well tuned to treat typical proteins, for ligands they can be problematic. In fact, typically applications of fragment-based methods to biochemical systems, for example, to protein-ligand binding, are based on performing a few single point calculations for structures obtained at a lower level of theory (such as with force fields). Although these methods have been applied to refine the energetics of some enzymatic reactions, they are usually not efficient enough to allow for many hundreds of single point calculations needed to map out a reaction path for a system containing thousands of atoms, although geometry optimizations of large systems can be performed for systems consisting of several hundreds of atoms, ,, вЂ“. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Д¬ompeting interests: The authors have declared that no competing interests exist.ДЇragment-based quantum mechanical methods вЂ“ are becoming increasingly popular, and have been used to describe a very diverse set of molecular properties for large systems. DF thanks the Next Generation Super Computing Project, Nanoscience Program (MEXT, Japan) and Strategic Programs for Innovative Research (SPIRE, Japan) for funding. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ДЇunding: CS was funded by IRENE.

Received: DecemAccepted: FebruPublished: April 12, 2013Д¬opyright: В© 2013 Steinmann et al. PLoS ONE 8(4):Д®ditor: Freddie Salsbury, Wake Forest University, United States of America Citation: Steinmann C, Fedorov DG, Jensen JH (2013) Mapping Enzymatic Catalysis Using the Effective Fragment Molecular Orbital Method: Towards all ab initio Biochemistry.

Casper xoxo 2011 rapidshare