One may find here some preprints of my papers,
general descriptions of my current and past projects as
well as various additional informations. By definition
this page is going to be under construction all the time - sorry for problems
while viewing it.
2. Computational Biology - large bio-molecules
Proteins are chains of aminoacids
linked by the petide bond. They play fundamental role in all biological
systems. A summary of my first encounters with proteins you may find
below.
1. Computer Simulations of CO photodissociated from myoglobin
The fundamental role of myoglobin
and haemoglobin in understanding of protein
structure and function, follows from their well defined structural
and spectroscopical features, manifesting during conformational changes
associated with their physiological functions (Karplus 1972). These globin
proteins are responsible for currying and storage of oxygen in vertebrate
organisms, due to the ability of binding small ligands to the haem prostetic
groups that form their active
sites. Upon binding or dissociating a ligand, both myoglobin
and haemoglobin undergo a series of characteristic structural transitions,
that have been extensively studied using various experimental techniques
and computer simulations (Kuczera 1997).
Recent experimental advances allowed a more detailed description of
some aspects of ligand binding reaction and ligand and protein dynamics
after photodissociation. Low temperature x-ray (Hartmann et. al. 1996,
Schlichting et. al. 1994, Srajer et. al. 1996) and room temperature infrared
femtosecond time-resolved studies (Lim et. al. 1995a, 1995b, 1997) of the
photolyzed state of the carbonmonoxy-myoglobin (MbCO) revealed that the
CO is confined to a small region of the myoglobin haem
pocket, with the parallel orientation with respect to the haem
plane.
Based on those findings Lim, Jackson and Anfinrud (Lim et. al. 1995a)
suggested a model of a docking site, enforcing due to steric
interactions, unfavorable for rebinding, parallel with respect to the haem
plane orientation of carbon monoxide. The existence of such docking
site for CO, could possibly explain the ability of haem proteins to discriminate
between binding of O_2 and CO. It is known that while a free haem binds
CO molecule about 1000 times stronger then O_2 molecule, in the haem proteins
this ratio is reduced approximately 50 times (Springer et. al. 1994).
Photodissociation of carbon monoxide from fully solvated sperm whale
myoglobin and its Phe29 mutant is studied using classical molecular
dynamics simulation in [1]. Particle Meshed Ewald (PME) algorithm is employed
to account for the long range electrostatic interactions in the framework
of standard periodic boundary condition simulation protocol. The
CO distribution in the haem pocket after dissociation is investigated and
the results are compared to the recent experimental and theoretical findings.
Two different models of photodissociation are compared. It is found
that on average the ligand is confined to a small part of the haem pocket
around the low temperature x-ray positions (Hartmannet. al. 1996),
with almost parallel orientation with respect to the haem plane,
in agreement with the recent experimental studies using femtosecond time-resolved
infrared absorption spectroscopy (Lim et. al. 1995a).
The impact of point mutation Phe29, as well as the different choice
of simulation box are discussed. The point mutation Leu29 -> Phe29
does not influence significantly the angular and spatial distribution of
CO in the haem pocket. The haem relaxation, as measured by the displacement
of the haem iron atom with respect to the haem plane, is found to be essentially
completed within the first 3 ps.
[1] J.Meller and R.Elber; Computer Simulations of Carbon
Monoxide Photodissociation in
Myoglobin: Structural Interpretation of the B states, Biophysical
Journal, in press (1998)
1. Folding of a small peptide: path integral technique using the Onsager-Machlup action
A novel formulation to compute classical trajectories at long time has
been introduced by Elber.
It is based on stochastic path formulation and employs a nonlinear
optimization of an action [1]. The optimization is numerically stable for
almost an arbitrary time step. It makes it possible to
calculate condense phase trajectories of very long times. The formalism
provides approximate solutions to the Newton equations in which the high
frequency motions are filtered out.
The folding pathways of C-peptide
from an extended chain configuration to an alpha helix are examined using
the new formalism. The computations employ an extended atom picture of
the peptide (CHn groups are modeled as point masses) and an explicit solvent
model (a periodic box of TIP3P
water molecules). Ten folding trajectories will be presented and discussed
[2].
[1] Roberto Olender and Ron Elber, "Calculation of classical
trajectories with a very large time step: Formalism and numerical
examples", J. Chem. Phys. 105,9299(1996)
[2] Ron Elber and Jaroslaw Meller, to be published