Drug Discovery Research Center

Preamble

Drug Discovery Research Center

Every disease starts at the molecular level. Thus, ultimately ever cure has to be achieved at the molecular level. This recognition leads us inevitably to the direction of Molecular Medicine.

A great deal of progress is expected to occur after the completion of the Human Genome Project. However, even if all the possible information is extracted from the genes, it does not give us the 3D structure of proteins. Thus, we still have no information as to the folding to a functional form, of enzymes and receptors, among many other biologically important molecular arrays. Beyond such basic information, one would also need to know how drug molecules are complexed with these enzymes and receptors.

Finally, some additional mechanistic information related to pre- or post-complexation metabolic reactions, may also be needed. Even though some experimental techniques (X-Ray, NMR, etc.) are available, in the future more and more computations will be used to generate increasingly more accurate results, for a decreasing expense. This will eventually open up a new avenue: Computational Molecular Medicine.

We are eager to integrate our results with biochemical and molecular-biological data, either collected in our laboratory or available through collaboration with specialists in the field. There are always biological structures undergoing computational studies in the laboratory.

Summer School 2009

The Future of Computations - Computations of the Future

Summer School / Workshop

14^th June - 5^th July 2009

Purpose: The purpose of this Summer School/Workshop is to help students to produce publishable papers in peer-reviewed internationally recognized journals of relatively high impact factor (IF>1.0)

Duration: Five weeks long in the summer of 2009. The exact starting date will be determined according to the dates of the final examinations of those Universities where the students are coming from.

Molecular Information

J. Phys. Chem. A, 110 (49), 13325 -13331, 2006.

Thermodynamic Functions of Conformational Changes: Conformational Network of Glycine Diamide Folding, Entropy Lowering, and Informational Accumulation

Szilard N. Fejer, Imre G. Csizmadia, and Bela Viskolcz*

A possible folding and missfolding explanation of a single point mutation in human galactokinase - A combined theoretical study

Molecular dynamics calculations (MD) were performed (10 ns) for the wild‑type (WT) and the Pro²⁸Thr point mutated (MT) human galactokinase enzyme (GALK1). Comparative analysis of the equilibrated trajectory (last 4 ns) revealed, in different global motions, compared the WT and MT forms of GALK1. The explanation of this behavior was found to be the alteration of the local interaction sites.

Performance of the general amber force field in modeling aqueous POPC membrane bilayers.

Jójárt B, Martinek TA.

Peptid Research

The proprties of the peptide conformations are the key information to better understand the protein folding. We will focus in our studies the molecular information contents. The effect of the point mutation on the structural changing of polypeptides and proteins is the other main stream of our study.

The Future of Computations - Computations of the Future

Számítások Jövője - Jövő Számításai

„Gyógyszertervezés új irányai - New Directions in Drug Designs"

Workshop Program

2008. május 22.

Szegedi Tudományegyetem Pedagógusképző Kar Díszterem

(Szeged, Boldogasszony sgt. 6)

The Future of the Drug Discovery Process and the

Fate of the Pharmaceutical Industry

"We can't solve problems

by using the same thinking we used when we created them"

Albert Einstein

Executive Summary

In accordance with the structure of Scientific Revolutions the Pharmaceutical Industry ran into "dead-end streets" several times during its modern history. Such problematic periods were followed by a new Renaissance which was due to a new mode of thinking, the application of a new philosophy, amounting to nothing less than a characteristic Paradigm-shift. The acceptance of the paradigm-shift, and the application of its associated new technology, resulted in a corresponding Breakthrough, at every time. We may assign, to these happenings, approximately, the following years, with ±5 year tolerance: 1890s, 1920s, 1950s, 1980s, thus, these breakthroughs occurred in roughly 30 years of intervals. Clearly, we are facing a new Breakthrough, in the near future, perhaps in 2010 or soon thereafter.

Those who will act as midwives for the birth of the new technology can take advantage of the emerging new Molecular Revolution. In essence, their advanced knowledge will allow them to apply the new technology before anybody else does, thus, they can become leaders of a multi-trillion-dollar Pharmaceutical Industry

Possible dynamic anchor points in a benzoxazinone derivative-human oxytocin receptor system - a molecular docking and dynamics calculation

Balázs Jójárt, Árpád Márki

Preamble