1999 Progress Report: BESS, A System For Predicting The Biodegradability Of New CompoundsEPA Grant Number: R826114
Title: BESS, A System For Predicting The Biodegradability Of New Compounds
Investigators: Punch, William F.
Institution: Michigan State University
EPA Project Officer: Klieforth, Barbara I
Project Period: November 1, 1997 through October 31, 2000
Project Period Covered by this Report: November 1, 1998 through October 31, 1999
Project Amount: $285,063
RFA: Technology for a Sustainable Environment (1997) RFA Text | Recipients Lists
Research Category: Sustainability , Pollution Prevention/Sustainable Development
Objective:The objective of this work is to further develop a software system called Biodegradation Evaluation and Simulation System (BESS) that can predict the biodegradability of a compound based on the structural features of that compound and the prevailing environmental conditions. The approach pursued in the development of BESS is based on the iterative use of plausible enzymatic transformations that are hierarchically organized based on knowledge of microbial physiology and ecology. This organization reduces the potentially large number of enzymatic transformations that could apply to a compound, making the approach computationally feasible. Only those enzymatic transformations that are most likely to provide anabolic intermediates or energy to microorganisms, and thus, have evolved through processes of natural selection are used, further reducing complexity.
The development of BESS software that employs a fundamentally different approach to the prediction of whether a given chemical will undergo biodegradation in the environment was initiated previously. The approach is based on the simulated application of plausible enzymatic transformations in an iterative manner. The enzymatic transformations are organized hierarchically, reflecting knowledge about the likelihood of any enzyme being applied. Such organization reduces the potentially large number of enzymatic transformations that could apply, concentrating instead on those rules that are most likely to provide anabolic intermediates or energy (or some other benefit to microorganisms), and thus have evolved through the processes of natural selection. Rules for a limited number of chemical classes have been codified, and prototype software has been developed that is capable of correctly simulating the biodegradation of chemicals for which rules have been entered. A user interface has been developed that permits the user to review the proposed path of degradation step-by-step, modify or enter rules to explore "what if" scenarios, and identify metabolites that may accumulate in the environment. The proposed research will: (1) expand the number and kinds of enzymatic transformations that are codified; (2) develop and test a rule hierarchy; and (3) use genetic algorithms as a tool to "discover" rules that suggest as-of-yet unencoded, or even undiscovered pathways, giving the system a great deal of robustness in dealing with novel compounds.
The proposed research will further develop BESS, which can predict whether a specific compound is likely to undergo biodegradation in the environment. BESS would serve at least three functions: (1) the use of BESS would allow biodegradability to be considered early in the product development process; (2) BESS could be used by regulatory agencies to guide decisions regarding proposed regulation and testing; and (3) BESS could be used as a tutorial to teach users which features of chemicals or the environment restrict or promote biodegradation. A compilation of plausible biodegradation rules, independent of BESS, will constitute an important resource for environmental scientists.
Progress Summary:The BESS code is functional and running on a Web server at Michigan State University. The core of the BESS code is run on a server at the university, on a machine of sufficient power to be able to run nearly any query. Access to the server is provided as a java applet that can be run anywhere on a java-capable browser, which creates a very portable system that is, at the same time, centrally controlled and much faster than the previous version. The reimplemented core routines, now written in C++, are about 10 times faster, providing room for growing the rulebase. The core code does not have to be distributed, providing much better control of BESS. The fact that the graphic user interface (GUI) is via a java applet means that it is quite portable and easily available to anyone who knows the Web address.
The code was prototyped, but it has been difficult to get fully running, and only recently has been brought online. The work of adding rules to BESS has made some progress. Overall, about 100 patterns are now in BESS; more are expected this year as researchers have an opportunity to improve it.
The present BESS works only with simplified molecular input line entry specifications (SMILES) strings; however, this has proven to be somewhat of a hindrance to project collaborators, as they would prefer 2D/3D visualization of the rules. Public domain (PD) software to convert SMILES to Molfiles or other more common formats, which can then be displayed using Micro Dynamics, Ltd. (MDL) plugins in Netscape or Internet Explorer, are being explored.