TITLE:
The LBFGS quasi-Newtonian method for molecular modeling prion AGAAAAGA amyloid fibrils
AUTHORS:
Jiapu Zhang, Yating Hou, Yiju Wang, Changyu Wang, Xiangsun Zhang
KEYWORDS:
Protein 3D Structure; Computational Approaches; Optimization Method; Molecular Modelling; Prion AGAAAAGA Amyloid Fibrils
JOURNAL NAME:
Natural Science,
Vol.4 No.12A,
December
31,
2012
ABSTRACT: Experimental
X-ray crystallography, NMR (Nuclear Magnetic Resonance) spectroscopy, dual
polarization interferometry, etc. are indeed very powerful tools to determine
the 3-Dimensional structure of a protein (including the membrane protein);
theoretical mathematical and physical computational approaches can also allow
us to obtain a description of the protein 3D structure at a submicroscopic
level for some unstable, noncrystalline and insoluble proteins. X-ray
crystallography finds the X-ray final structure of a protein, which usually
need refinements using theoretical protocols in order to produce a better
structure. This means theoretical methods are also important in determinations
of protein structures. Optimization is always needed in the computer-aided drug
design, structure-based drug design, molecular dynamics, and quantum and
molecular mechanics. This paper introduces some optimization algorithms used in
these research fields and presents a new theoretical computational method—an
improved LBFGS Quasi-Newtonian mathematical optimization method—to produce 3D
structures of prion AGAAAAGA amyloid fibrils (which are unstable,
noncrystalline and insoluble), from the potential energy minimization point of
view. Because the NMR or X-ray structure of the hydrophobic region AGAAAAGA of
prion proteins has not yet been determined, the model constructed by this paper
can be used as a reference for experimental studies on this region, and may be
useful in furthering the goals of medicinal chemistry in this field.