research

Molecular automata assembly: principles and simulation of bacterial membrane construction

In order to understand the basic rules and principles governing molecular self-assembly we introduced a new approach - molecular automata - modeling and simulating molecular self-assembly [13]. Also we introduced the concept of molecular programming to simulate the biological function or operation performed by an assembled molecular state machine. The method is illustrated modelling Escherichia coli membrane [12] construction including the assembly and operation of ATP synthase as well as the assembly of the bacterial flagellar motor. Flagellar motor operation was simulated using a different approach based on state machine definition used in virtual reality systems. The proposed methodology provides a modelling framework for simulation of biological functions performed by cellular components and other biological systems suitable to be modelled as molecular state machines (Watch the video clip).

'Evolving hardware' as model of enzyme evolution

Organism growth and survival is based on thousands of enzymes organized in networks. The motivation to understand how a large number of enzymes evolved so fast inside cells may be relevant to explaining the origin and maintenance of life on Earth. We introduced electronic circuits called ‘electronic enzymes’ that model the catalytic function performed by biological enzymes [14].

Electronic enzymes are the hardware realization of enzymes defined as molecular automata with a finite number of internal conformational states and a set of Boolean operators modelling the active groups of the active site. One of the main features of electronic enzymes is the possibility of evolution finding the proper active site by means of a genetic algorithm yielding a metabolic ring or k-cycle that bears a resemblance to Krebs (k=7) or Calvin (k=4) cycles present in organisms. The simulations are consistent with those results obtained in vitro evolving enzymes based on polymerase chain reaction (PCR) as well as with the general view that suggests the main role of recombination during enzyme evolution. The proposed methodology [14] shows how molecular automata with evolvable features that model enzymes or other processing molecules provide an experimental framework for simulation of the principles governing metabolic pathways evolution and self-organization.

Molecular automata modeling in structural biology

Dynamic activities within living cells rest on biomolecular systems organized into cellular structures and organelles. A common motivation of computer simulation in the past decade has been to understand cellular complexity by developing models from which to derive powerful unifying generalizations and predictions of cell dynamics. However, the modeling and simulation of cell dynamics present a host of theoretical and practical challenges. These challenges involve the need to achieve some level of competence in cellular and molecular principles (i.e., enzymology, polymerization, self-assembly) as well as familiarity with computer simulation and mathematical methods (i.e., programming, graphics rendering, differential equations, numerical analysis). Cellular automata are discrete space and time models that have been used to model biological systems. A cellular automaton in two dimensions, roughly speaking, is a checkerboard, where each cell is called a finite automaton because the cell is in any of a finite number of states. This chapter [13] discusses molecular automata modeling in structural biology.