Author:
Corrado Giannantoni
Affiliation:
ENEA - Casaccia Research Center, Italy
Keyword(s):
Protein folding, Complex systems dynamics, Traditional Differential Calculus (TDC), Incipient Differential Calculus (IDC), Molecular docking, Drug design.
Related
Ontology
Subjects/Areas/Topics:
Bioinformatics
;
Biomedical Engineering
;
Pharmaceutical Applications
Abstract:
The relevance of Protein Folding is widely recognized. It is also well-known, however, that it is one of the dynamic problems in TDC considered as being intractable. In addition, even in the case of solutions obtainable in reasonable computation time, these always present a “drift” between the foreseen behavior of the biological system analyzed and the corresponding experimental results. A drift which is much more marked as the order of the system increases.
Both the “intractability” of the problem and the above-mentioned “drifts”, as well as the insolubility of the problem in explicit terms (or at least in a closed form), can be overcome by starting from a different gnoseological approach. This suggests a new definition of derivative, the “incipient” derivative.
The solution to the “Three-body Problem” obtained by means of IDC, and its extension to any number of bodies, allows us to assert that the folding of even a macroscopic protein, such as dystrophin for example, made up of
about 100,000 atoms, can be carried out in a few minutes, when the model is run on next generation computers (1 Petaflop).
The same methodology can also be applied to both Molecular Docking and computer-aided Drug Design.
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