[SCAN] Studying biomedically relevant systems by molecular simulation

Scan Seminar

Title: Studying biomedically relevant systems by molecular simulation

Speaker: António Baptista

From: Molecular Simulation Lab, ITQB

Abstract:

The detailed conformational characterization of molecules of biomedical
interest is often a challenging and difficult task using experimental
techniques. Valuable insight about those molecules and their mode of
action can be obtained by molecular simulation methodologies, as
illustrated here for three different kinds of system: a small peptide, a
protein and a synthetic molecule. The peptide investigated is kyotorphin,
a small endogenous neuropeptide of analgesic action that binds to a
still-unknown specific receptor my means of a membrane-mediated process;
our study suggest that its conformation is optimized for binding upon
association with the membrane and that, somewhat surprisingly, its charge
is not affected by membrane internalization. The protein investigated is
the human prion, associated with the Creutzfeldt-Jakob disease and other
amyloid pathologies; our study of its pH-induced misfolding identifies the
C-terminal domain as being the most affected and leads us to propose a
misfolding intermediate. The synthetic molecules investigated are peptide
dendrimers, a new class of tree-like molecules composed of aminoacids; our
study of several dendrimers potentially binding vitamin B12 indicates the
lack of a predominant folded conformation and finds net charge as a major
determinant of compactness. These three studies illustrate how molecular
simulation methods can complement experimental data by providing new
working hypotheses.