A regularized and renormalized electrostatic coupling Hamiltonian for hybrid quantum-mechanical-molecular-mechanical calculations.

We describe a regularized and renormalized electrostatic coupling Hamiltonian for hybrid quantum-mechanical (QM)-molecular-mechanical (MM) calculations. To remedy the nonphysical QM/MM Coulomb interaction at short distances arising from a point electrostatic potential (ESP) charge of the MM atom and also to accommodate the effect of polarized MM atom in the coupling Hamiltonian, we propose a partial-wave expansion of the ESP charge and describe the effect of a s-wave expansion, extended over the covalent radius r(c), of the MM atom. The resulting potential describes that, at short distances, large scale cancellation of Coulomb interaction arises intrinsically from the localized expansion of the MM point charge and the potential self-consistently reduces to 1r(c) at zero distance providing a renormalization to the Coulomb energy near interatomic separations. Employing this renormalized Hamiltonian, we developed an interface between the Car-Parrinello molecular-dynamics program and the classical molecular-dynamics simulation program Groningen machine for chemical simulations. With this hybrid code we performed QM/MM calculations on water dimer, imidazole carbon monoxide (CO) complex, and imidazole-heme-CO complex with CO interacting with another imidazole. The QM/MM results are in excellent agreement with experimental data for the geometry of these complexes and other computational data found in literature.

New developments in applying quantum mechanics to proteins.

Algorithmic improvements of quantum mechanical methodologies have increased our ability to study the electronic structure of fragments of a biomolecule (e.g. an enzyme active site) or entire biomolecules. Three main strategies have emerged as ways in which quantum mechanics can be applied to biomolecules. The supermolecule approach continues to be utilized, but it is slowly being replaced by the so-called coupled quantum mechanical/molecular mechanical methodologies. An exciting new direction is the continued development and application of linear-scaling quantum mechanical approaches to biomolecular systems.

Computational prediction of the three-dimensional structures for the Caenorhabditis elegans tubulin family.

In this article we characterize, from a structural point of view, all 16 members of the tubulin gene family of Caenorhabditis elegans (9 alpha-tubulins, 6 beta-tubulins, and 1 gamma-tubulin). We obtained their tertiary structures by computationally modifying the X-ray crystal structure of the pig brain alpha/beta-tubulin dimer published by Nogales et al. [Nature (London) 1998;391:199-203]. Our computational protocol involves changing the amino acids (with MIDAS; Jarvis et al., UCSF MIDAS. University of California, San Francisco, 1986) in the 3D structure of pig brain alpha/beta-tubulin dimer followed by geometry optimization with the AMBER force field (Perlman et al., AMBER 4. University of California, San Francisco, 1990). We subsequently analyze and compare the resulting structures in terms of the differences in their secondary and tertiary structures. In addition, we compare the pattern of hydrogen bonds and hydrophobic contacts in the guanosine triphosphate (GTP)-binding site for all members of the tubulin family. Our computational results show that, except for gamma-tubulin, all members of the C. elegans tubulin family have similar secondary and 3D structures and that the change in the pattern of hydrogen bonds in the GTP-binding site may be used to assess the relative stability of different alpha/beta-tubulin dimers formed by monomers of the tubulin family.