Chemistry Reference
In-Depth Information
and cloud computing. For algorithm design there is also the problem of wasting
time waiting for other slaves to finish their tasks. Another algorithm to get better
protein-ligand binding solutions consists of using migration and pattern reduction
operators to filter out the worst search directions.
The rate of future growth of chemical/biological/compound/target information is
unpredictable. The present size of some of the databases is astonishing, containing
10
7
compounds. Despite duplicate entries and different types of molecular
representations for the same compound, the number of compounds in databases is
very large. Biological activity of the molecules is also very large, containing
millions of compounds with activities against 10
4
targets. There has also been
considerable growth for biological target information including candidate protein
coding genes for therapeutic exploration [479-486].
CONFIDENCE AND THE FUTURE
It is important to understand the errors involved in calculating drug-protein
interactions,
i.e.
energetics of drug discovery for pharmaceutical research. A hit
lead (drug candidate compound) has micro molar concentration and nano molar
activity. A drug lead should act in a realm perhaps less than 0.5 kcal/mol [487-
491].
Compared to quantum mechanics, force fields are rather simple tools,
approximations that allow forces and energies to be quickly calculated. Included are
dihedral and torsion interactions, electrostatic and van der Waals interactions
between atoms. Of the 6-12 Lennard-Jones equation (van der Waals interaction
energy), the '12' repulsive term is supposedly a too severe computational
convenience. The calculation convenience in the spherical shape of atoms
approximation does not hold for tight contacts. Simple, convenient point charges
which are atom centered, have their dependencies and error of fit.
Complex/time/effort/calculation difficulties are involved and improved
parameterization are required for more rigor in the approaches. The simple methods
made it possible for us to move forwards with larger steps in reasonable time,
despite being crude approximations. Determination of molecular structures can be
obtained by force fields at a reasonable level. They are however, not so good in the
determination of energies.
