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Stewart, James

Address

15210 Paddington Cir
Colorado Springs, CO, 80921-2512
USA

UEI: N/A

Number of Employees: N/A

HUBZone Owned: No

Woman Owned: No

Socially and Economically Disadvantaged: No

SBIR/STTR Involvement

Year of first award: 1993

Phase I Awards

Phase II Awards

75%

Conversion Rate

$363,567

Phase I Dollars

$1,834,942

Phase II Dollars

$2,198,509

Total Awarded

Awards

Up to 10 of the most recent awards are being displayed. To view all of this company's awards, visit the Award Data search page.

Migrate enzyme modeling technology from development site to experimental research

Amount: $458,294 Topic: 300

Project Summary Abstract The rate of progress in developing new pharmaceuticals could be accelerated if experimental researchers had practical methods for modeling enzyme mechanisms Unfortunately all current programs have severe limitations either being too slow too complicated or too inaccurate Although an efficient and accurate method for modeling mechanisms in enzyme catalyzed reactions has been developed and made available in the form of the stand alone program MOPAC very few users of this program have used it for that purpose Instead most users have used it for modeling simpler systems such as the docking of substrates into active sites in enzymes This reluctance by experimentalists to model enzyme mechanisms can be attributed to the severe learning curve barrier currently necessary before useful results can be obtained Experimentalists want to focus on the chemistry involved and as far as possible do not want to become involved in computational details software requirements restrictions etc As a result tools that can be used efficiently by computational chemists are being essentially ignored by experimentalists despite the fact that if they were used they would be enormously valuable for modeling postulated reactions to determine their feasibility This project aims to reduce the size of this learning barrier by making MOPAC easier to use by developing documentation to describe what can be done the issues involved methods and strategies for exploring models of enzyme mechanisms and by providing several complete worked examples including the chymotrypsin catalyzed hydrolysis of a peptide bond The approach would begin with a small research project to map out the chymotrypsin mechanism Any software problems encountered would be addressed at this point Various strategies for exploring the mechanism would be examined and using the results a recommended set of procedures would be generated as documentation for use by experimentalists Experimentalists would then use the resulting program and documentation to model reactions and phenomena in systems of interest and their feedback would be used in improving the product A few cycles of modeling and feedback would yield a product that should be an acceptable tool for the experimental research community for modeling enzyme mechanisms Project Narrative The task of designing new pharmaceuticals can be aided by a computer assisted model of enzyme mechanism that would be easy to use A program to do this MOPAC already exists but currently it is only being used by expert computational chemists The objective is to modify the MOPAC program and its documentation to make it suitable for use by experimentalists

SBIR

Phase II

2015

HHS

NIH

Migrate enzyme modeling technology from development site to experimental research

Amount: $113,567 Topic: NIGMS

OCR issue PUBLIC HEALTH RELEVANCE Project Narrative The task of designing new pharmaceuticals can be aided by a computer-assisted model of enzyme mechanism that would be easy to use. A program to do this, MOPAC2012, already exists, but currently it is only being used by expert computational chemists. The objective is to modify the MOPAC2012 program and its documentation to make it suitable for use by experimentalists.

SBIR

Phase I

2014

HHS

NIH

Computer Modeling of Biochemical Reaction Rates

Amount: $626,648

DESCRIPTION (provided by applicant): An accurate and rapid computational method for predicting reaction rates for biochemical processes would be developed as a tool for biochemistry research. Existing semiempirical methods, while rapid, are not sufficiently accurate. The recently completed PM6 method has increased the accuracy of prediction of heats of formation of stable ground-state systems, but is still not accurate for predicting transition state energies. The proposed work would involve developing a method specifically designed for predicting activation barriers. This would involve the construction of a database of activation barriers. Existing semiempirical methods use a consistent set of parameters in predicting geometries and energies. In the new approach, Geometries would be predicted using PM6, and energies would be less elegant than conventional methods it would allow activation barriers to be predicted with much better accuracy. Construction of the database of activation barriers would involve using results of very high-level ab-initio calculations. Other groups have done calculations of this type, so this step would involve only literature research. Development of the new method involves parameter optimization only. The issues involved are now well understood, and available optimization programs should be sufficient. Finally, the new method would be integrated into existing commercial program MOPAC2009, which would be re-named MOPAC2011. PUBLIC HEALTH RELEVANCE: The work to be done involves developing a method to predict accurately the size of reaction barriers, giving an indication of which biochemical processes are feasible.

SBIR

Phase II

2009

HHS

NIH

Computer modeling of Biochemical Reaction Rates

Amount: $100,000

DESCRIPTION (provided by applicant): An accurate and rapid computational method for predicting reaction rates for biochemical processes would be developed as a tool for biochemistry research. Existing semiempirical methods, while rapid, are not sufficient ly accurate. The recently completed PM6 methods, while rapid, are not sufficiently accurate. The recently completed PM6 method has increased the accuracy of prediction of heats of formation of stable ground-state systems, but is still not accurate for pr edicting transition state energies. The purposed work would involve developing a method specifically designed for predicting activation barriers. This would involve the construction of a database of activation barriers, and using that database to optimize parameters to reproduce the activation barriers. Existing semiempirical methods use a consistent set of parameters in predicting geometries and energies. In the new approach, geometries would be predicted using PM6, and energies would be predicted using the proposed method. Although this two-step procedure would be less elegant than conventional methods if would allow activation barriers to be predicted with much better accuracy. Construction of the database of activation barriers would involve using res ults over very high-level ab-initio calculations. Other groups have already done calculations of this type, so this step would involve only literature research. Development of the new method involves parameter optimization only. The issues involved are n ow well understood, and available optimization programs should be sufficient. Finally, the new method would be integrated into the existing commercial program MOPAC2007.

SBIR

Phase I

2008

HHS

NIH

Computer Modeling of Biomolecular Systems

Amount: $750,000

SBIR

Phase II

2004

HHS

NIH

Computer Modeling of Biomolecular Systems

Amount: $100,000

DESCRIPTION (provided by applicant): Software for full quantum mechanics modeling of biological macromolecules that is both fast and accurate is proposed. Cancer researchers could use this software to model protein and enzyme structure as well as enzyme reactions involving bond formation and breaking. The software would be based on a semi-empirical quantum chemical compute engine with a newly developed parameterization for all biological elements including the six principal transition elements. In this Phase I proposal, the question of whether an accuracy of 3 kcal/mol can be achieved for biological systems will be answered. If this answer is affirmative, the following tasks will be pursued in Phase II: A. Methods specific to proteins and other biomolecules would be developed. Existing methods are (a) too general, and (b) unsuitable for biochemical work, due to the lack of transition metals. By developing semiempirical methods that are specific to systems found in biochemistry, an increase in accuracy can be obtained, thus the average error in semiempirical methods should be decreased by about 60% relative to PM3. Similarly, limiting the range of properties optimized for transition metals to those found in biochemical systems, an accuracy at least equivalent to ab initio 6-31g would be achieved. B. Writing Graphical user interfaces (GUI) and utilities to allow reactions, transition states, UVVisible spectra, etc. to be modeled. These will allow users to run simulations using by issuing "requests", which the GUI will convert into commands for the compute engine. The compute engine would run at a speed sufficient to allow real-time simulations to be performed. This tool will be useful for visualizing biochemical systems, and for understanding the mechanisms involved.

SBIR

Phase I

2003

HHS

NIH

Development of AM1 Semi-Empirical Parameters for the Group III, V, and VI Elements

Amount: $50,000

Reference data abstracted from literature sources, such as NIST and JANAF, as well as original research publications, will be used in the construction of data-sets. These data-sets will be suitable for use in parameterizing elements at the AM1 level, and, with appropriate modification, for parameterizing elements for other semiempirical methods. As several elements in Groups III, V, and VI have already been successfully parameterized at the AM1 level, and as the amount of reference data for some elements is known to be very small, the focus of this work will be on the elements Gallium, Arsenic, Selenium, Antimony and Tellurium. An attempt will be made to develop a working set of parameters in order to determine the feasibility of more complete parameterizations. The results of earlier parameterization projects indicated that a two-way dialog between the research group carrying out the parameterization and field users of the parameter sets is essential.

SBIR

Phase I

1993

DOD

ARMY