Using established methods of knowledge representation and rule- based expert systems I propose to develop a symbolic simulation of DNA metabolism. Rule-based expert systems permit simulations of DNA metabolism which can predict the activity of both individual enzymes and of entire pathways under a wide variety of physiological conditions. Both classical production rules and an assumption-based truth maintenance system will be used. Rule-based methods have the intrinsic property of being able to explain conclusions using English sentences or graphic representations of the pattern of inference. The enzymes, substrates and products will also be represented in a frame-based knowledge system. Knowledge based systems facilitate the description of product-precursor relationships between different metabolites as well as the complete pathway. Physiological conditions such as the presence of salts, nucleotides, temperature, ionic strength, pH, etc. will be presented graphically as active images of thermometers, gauges and switches. All environmental and substrate conditions can be changed by using a mouse pointing device. In response to changes of any parameter, a series of rules defining the specificity and reactivity of enzymes are automatically invoked and specific conclusions are made. The methods for specifying the actions of enzymes are well defined, allowing ready simulation of other enzymes. Simulations of individual enzymatic steps can be coupled together to generate a discrete event simulation of the entire metabolic pathway.
| Brutlag, D L; Galper, A R; Millis, D H (1991) Knowledge-based simulation of DNA metabolism: prediction of enzyme action. Comput Appl Biosci 7:9-19 |
