170 COMPUTER HARDWARE, SOFTWARE
the actual angle of rotation of each atom every 2 ps. Lastly, the applied torque
and rotation angles were averaged over all 126 residues (ISP residues 73 – 196),
and they were analyzed for individual residues as well.
The reference 22 researchers found that a water channel opened up, involv-
ing a number of critical amino acid residues, between the internal water mol-
ecules and the bulk, solvent water layer. As the ISP protein rotated during the
simulation, many critical hydrogen bonds were broken and reformed between
different amino acid residues. The authors suggest that their simulations have
relevance to the mechanism by which cytochrome bc 1 complex carries out
binding and reduction of substrate ubiquinone at the Q 0 site. Removal of
stigmatellin from the model, followed by the SMD simulation, mimics the
process by which product would be removed from the active site. Conversely,
docking of the ISP in its proximal conformation (close to heme b L ) in the
presence of stigmatellin mimics the formation of the active complex with
substrate. The authors also believe that hydrogen bonding within the active
site plays a major role in positioning the ISP and substrate. As the reader will
note from the preceding discussion, the major portion of a molecular dynamics
study must be the laborious preparation of the model, so that possible, or
probable, mechanistic details can be discovered for complex protein systems
such as cytochrome bc 1.
4.4 QUANTUM MECHANICS - BASED
COMPUTATIONAL METHODS
4.4.1 Introduction,
Many other approaches for fi nding a correct structural model are possible.
A short description of ab initio, density functional and semiempirical methods
are included here. This information has been summarized from the paperback
Chemistry with Computation: An Introduction to Spartan.^29 The Spartan
program is described in Section 4.5. Another description of computational
chemistry including more mathematical treatments of quantum mechanical,
molecular mechanical, and statistical mechanical methods is found in the
Oxford Chemistry Primers volume: Computational Chemistry.^15
4.4.2 Ab Initio Methods,
Ab initio calculations are based on fi rst principles using molecular orbital
(MO) calculations based on Gaussian functions. Combinations of Gaussian
functions yield Slater - type orbitals (STOs), also called Slater determinants.
STOs are mathematical functions closely related to exact solutions for the
hydrogen atom. In their ultimate applications, ab initio methods would use
Gaussian - type wave functions rather than STOs. The ab initio method assumes
that from the point of view of the electrons the nuclei are stationary, whereas