BIOINORGANIC CHEMISTRY A Short Course Second Edition

166 COMPUTER HARDWARE, SOFTWARE

4.3.3 Biomolecule Modeling,

The modeling of biomolecules is discussed in reference 15, which provides
good background on protein folding, secondary protein structure prediction,
sequence alignment for fi nding comparable natural or synthetic proteins, and
modeling by homology to produce three - dimensional protein structures in
advance of their experimental elucidation. The last topic makes use of the
Ramachandran map that places protein structure into allowed conformational
regions for amino acids. Fitting of the modeled protein into allowed regions —
α - helical ( α ), β - strand ( β ) and left - handed helical (L) — indicates that the
protein conforms to known protein secondary structural constraints. Refer-
ence 15 includes a short discussion of theoretical investigations of enzyme
mechanism, useful for understanding the molecular basis of enzyme activity.
Karplus and Petsko have provided a review of the application of molecular
dynamics to biological problems.^16 Bioinorganic applications and examples of
molecular modeling studies discussed in reference 3 often are limited by the
lack of suitable small molecule analogs to the metal ion environments found
in metalloproteins. Two examples are the grossly distorted tetrahedral type I
Cu(II) sites in blue copper proteins and three - coordinate iron sites found in
the enzyme nitrogenase. Models for metalloporphyrin (hemoglobin, myoglo-
bin, cytochrome) active sites have been derived by modeling small molecules
and extending the AMBER^17 and MM2^18 force - fi eld parameterization schemes.
Learn more about AMBER at the website http://amber.scripps.edu/. A molec-
ular dynamics simulation of hydrogen peroxide binding to the heme iron in
cytochrome c peroxidase has been modeled using a modifi ed AMBER force

Figure 4.1 Conformational search procedures. (Adapted with permission from Figure
4.2 of reference 3a. VCH Publishers, Inc., New York and VCH Verlaggesellschaft mbH,
Weinheim, Federal Republic of Germany. Copyright 1995, VCH, Verlagsgesellschaft
mbH, Weinheim, Federal Republic of Germany.)

r

E

normal refinement

molecular dynamics

monte carlo

heating